Abstract
Ischemia-reperfusion (IR) injury is a damage to an organ when the blood supply is less than the demand required for normal functioning, leading to exacerbation of cellular dysfunction and death. IR injury occurs in different organs like the kidney, liver, heart, brain, etc., and may not only involve the ischemic organ but also cause systemic damage to distant organs. Oxygen-glucose deprivation in cells causes oxidative stress, calcium overloading, inflammation, and apoptosis. CREB is an essential integrator of the body’s various physiological systems, and it is widely accepted that dysfunction of CREB signaling is involved in many diseases, including ischemia-reperfusion injury. The activation of CREB can provide life to a cell and increase the cell’s survival after ischemia. Hence, GSK/CREB signaling pathway can provide significant protection to cells of different organs after ischemia and emerges as a futuristic strategy for managing ischemia-reperfusion injury. Different signaling pathways such as MAPK/ERK, TLR4/MyD88, RISK, Nrf2, and NF-κB, get altered during IR injury by the modulation of GSK-3 and CREB (cyclic AMP response element (CRE)–binding protein). GSK-3 (protein kinase B) and CREB are the downstream targets for fulfilling the roles of various signaling pathways. Calcium overloading during ischemia increases the expression of calcium-calmodulin-dependent protein kinase (CaMK), which subsequently activates CREB-mediated transcription, thus promoting the survival of cells. Furthermore, this review highlights the crosstalk between GSK-3 and CREB, promoting survival and rendering the cells resistant to subsequent severe ischemia.
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Abbreviations
- IR injury:
-
Ischemia-reperfusion
- CREB:
-
Cyclic AMP response element (CRE)-binding protein
- GSK-3β:
-
Glycogen synthase kinase 3-β
- CaMK:
-
Calcium-calmodulin-dependent protein kinase
- ATP:
-
Adenosine triphosphate
- PI3K:
-
Phosphoinositide-3-kinase
- NF-κB:
-
Nuclear factor-kappa B
- CBP:
-
CREB-binding protein
- DM:
-
Diabetes mellitus
- AD:
-
Alzheimer’s disease
- cGAS:
-
Cyclic GMP-AMP synthase
- STING:
-
Stimulator of interferon genes
- GPCR:
-
G-protein-coupled receptors
- RTK:
-
Receptor tyrosine kinase
- NMDA:
-
N-methyl-D-aspartate
- ROS:
-
Reactive oxygen species
- TNF-α:
-
Tumor necrosis factor-α
- IL-1β:
-
Interleukin-1β
- NO:
-
Nitric oxide (NO)
- TLR4:
-
Toll-like receptor
- PKC:
-
Protein kinase C
- PKA:
-
Protein kinase A
- CaMK:
-
Ca2+/CaM-dependent kinase
- HO-1:
-
Heme oxygenase 1
- SOD:
-
Superoxide dismutase
- TQ:
-
Thymoquinone
- APNp:
-
Adiponectin peptide
- DHPG:
-
Dihydroxyphenylglycine
- BBR:
-
Berberine
- CIG:
-
Cornel iridoid glycoside
- BCCAO:
-
Bilateral common carotid artery occlusion
- SCII:
-
Spinal cord ischemia-reperfusion injury
- BDNF:
-
Brain-derived neurotrophic factor
- DPP4:
-
Dipeptidyl peptidase4
- CUR:
-
Curcumin
- RISK:
-
Reperfusion injury salvage kinase
- TDZD-8:
-
4-Benzyl-2-methyl-1,2,4-thiazolidine-3,5-dione
- NMP:
-
Non-specific mitochondrial permeability
- LMWF:
-
Low-molecular-weight fucoidan
- KLF4:
-
Kruppel-like factor 4
- PACAP-Pituitary:
-
adenylate cyclase-activating polypeptide
- OLT:
-
Orthotopic liver transplantation
- OA:
-
Oleanolic acid
- LiCl:
-
Lithium chloride
- AST:
-
Astaxanthin
- DZ:
-
Daidzein
- LDH:
-
Lactate dehydrogenase
- MDA:
-
Malondialdehyde
- FXR:
-
Farnesoid X receptor
References
Abdel-Aleem GA, Khaleel EF, Mostafa DG, Elberier LK (2016) Neuroprotective effect of resveratrol against brain ischemia reperfusion injury in rats entails reduction of DJ-1 protein expression and activation of PI3K/Akt/GSK3b survival pathway. Arch Physiol Biochem 122(4):200–213. https://doi.org/10.1080/13813455.2016.1182190
Arora B, Khan H, Grewal AK, Singh TG (2023) Mechanistic insights on the role of nitric oxide in ischemia-reperfusion injury. In Nitric Oxide in Health and Disease 275–285 Academic Press. https://doi.org/10.1016/B978-0-443-13342-8.00004-1
Bai H, Zhao L, Liu H, Guo H, Guo W, Zheng L, Liu X, Wu X, Luo J, Li X, Gao L (2018) Adiponectin confers neuroprotection against cerebral ischemia-reperfusion injury through activating the cAMP/PKA-CREB-BDNF signaling. Brain Res 143:145–154. https://doi.org/10.1016/j.brainresbull.2018.10.013
Bangar A, Khan H, Kaur A, Dua K, Singh TG (2023) Understanding mechanistic aspect of the therapeutic role of herbal agents on neuroplasticity in cerebral ischemic-reperfusion injury. J Ethnopharmacol 117153. https://doi.org/10.1016/j.jep.2023.117153
Behl T, Kaur G, Sehgal A, Bhardwaj S, Singh S, Buhas C, Judea-Pusta C, Uivarosan D, Munteanu MA, Bungau S (2021a) Multifaceted role of matrix metalloproteinases in neurodegenerative diseases: pathophysiological and therapeutic perspectives. Int J Mol Sci 22(3):1413. https://doi.org/10.3390/ijms22031413
Behl T, Kumar K, Brisc C, Rus M, Nistor-Cseppento DC, Bustea C, Aron RA, Pantis C, Zengin G, Sehgal A, Kaur R (2021b) Exploring the multifocal role of phytochemicals as immunomodulators. Biomed Pharmacother 133:110959. https://doi.org/10.1016/j.biopha.2020.110959
Beker M, Dallı T, Elibol B (2018) Thymoquinone can improve neuronal survival and promote neurogenesis in rat hippocampal neurons. Mol Nutr Food Res 62(5):1700768. https://doi.org/10.1002/mnfr.201700768
Bell MT, Puskas F, Bennett DT, Herson PS, Quillinan N, Fullerton DA, Reece TB (2014) Dexmedetomidine, an α-2a adrenergic agonist, promotes ischemic tolerance in a murine model of spinal cord ischemia-reperfusion. J Thorac Cardiovasc Surg 147(1):500–507. https://doi.org/10.1016/j.jtcvs.2013.07.043
Beurel E, Grieco SF, Jope RS (2015) Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol Ther 148:114–131. https://doi.org/10.1016/j.pharmthera.2014.11.016
Ceulemans LJ, Verbeke L, Decuypere JP, Farre R, De Hertogh G, Lenaerts K, Jochmans I, Monbaliu D, Nevens F, Tack J, Laleman W (2017) Farnesoid X receptor activation attenuates intestinal ischemia reperfusion injury in rats. PLoS ONE 12(1):e0169331. https://doi.org/10.1371/journal.pone.0169331
Chang PM, Li KL, Lin YC (2019) Fucoidan–fucoxanthin ameliorated cardiac function via IrS1/Grb2/SOS1, GSK3β/CREB pathways and metabolic pathways in senescent mice. Mar Drugs 17(1):69. https://doi.org/10.3390/md17010069
Chen J, Wang W, Zhang Q, Li F, Lei T, Luo D, Zhou H, Yang B (2013) Low molecular weight fucoidan against renal ischemia-reperfusion injury via inhibition of the MAPK signaling pathway. PLoS ONE 8(2):e56224. https://doi.org/10.1007/s00424-018-2213-1
Chen R, Zhang YY, Lan JN, Liu HM, Li W, Wu Y, Leng Y, Tang LH, Hou JB, Sun Q, Sun T (2020) Ischemic postconditioning alleviates intestinal ischemia-reperfusion injury by enhancing autophagy and suppressing oxidative stress through the Akt/GSK-3β/Nrf2 pathway in mice. Oxid Med Cell Longev. https://doi.org/10.1155/2020/6954764
Chuang DM, Wang Z, Chiu CT (2011) GSK-3 as a target for lithium-induced neuroprotection against excitotoxicity in neuronal cultures and animal models of ischemic stroke. Front Mol Neurosci 4:15. https://doi.org/10.3389/fnmol.2011.00015
Corb Aron RA, Abid A, Vesa CM, Nechifor AC, Behl T, Ghitea TC, Munteanu MA, Fratila O, Andronie-Cioara FL, Toma MM, Bungau S (2021) Recognizing the benefits of pre-/probiotics in metabolic syndrome and type 2 diabetes mellitus considering the influence of akkermansia muciniphila as a key gut bacterium. Microorganisms 9(3):618. https://doi.org/10.3390/microorganisms9030618
Crack PJ, Wong CH (2008) Modulation of neuro-inflammation and vascular response by oxidative stress following cerebral ischemia-reperfusion injury. Curr Med Chem 15(1):1–4. https://doi.org/10.2174/092986708783330665
Das S, Cordis GA, Maulik N, Das DK (2005) Pharmacological preconditioning with resveratrol: role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation. Am J Physiol Heart Circ Physiol 288(1):H328–H335. https://doi.org/10.1152/ajpheart.00453.2004
Ding C, Han F, Xiang H, Wang Y, Li Y, Zheng J, Xue W, Ding X, Tian P (2019) Probiotics ameliorate renal ischemia-reperfusion injury by modulating the phenotype of macrophages through the IL-10/GSK-3β/PTEN signaling pathway. Pflug Arch Eur J Physiol 471:573–581. https://doi.org/10.1007/s00424-018-2213-1
Duarte-Silva E, Peixoto CA (2018) Molecular mechanisms of phosphodiesterase-5 inhibitors on neuronal apoptosis. DNA Cell Biol 37(11):861–865. https://doi.org/10.1089/dna.2018.4410
Engels J, Elting N, Braun L, Bendix I, Herz J, Felderhoff-Müser U, Dzietko M (2017) Sildenafil enhances quantity of immature neurons and promotes functional recovery in the developing ischemic mouse brain. Dev Neurosci 39(1–4):287–297. https://doi.org/10.1159/000457832
Evankovich J, Zhang R, Cardinal JS, Zhang L, Chen J, Huang H, Beer-Stolz D, Billiar TR, Rosengart MR, Tsung A (2012) Calcium/calmodulin-dependent protein kinase IV limits organ damage in hepatic ischemia-reperfusion injury through induction of autophagy. Am J Physiol Gastrointest Liver Physiol 303(2):G189–G198. https://doi.org/10.1152/ajpgi.00051.2012
Fan YD, Zhu ML, Geng D, Zhou K, Du GJ, Wang ZL (2018) The study on pathological mechanism and solution method for spinal cord ischemia reperfusion injury. Eur Rev Med Pharmacol Sci 22(13):4063–4068
Fan X, Zhao Z, Wang D, Xiao J (2020) Glycogen synthase kinase-3 as a key regulator of cognitive function. Acta Biochim Biophys Sin 52(3):219–230. https://doi.org/10.1093/abbs/gmz156
Fan J, Chen Y, Song J (2021) Sevoflurance combined with xenon pretreatment protects against spinal cord ischemia-reperfusion injury in a rat model. Chin J Tissue Eng Res 25(23):3660. https://doi.org/10.12307/2021.036
Feng J, Lucchinetti E, Ahuja P, Pasch T, Perriard JC, Zaugg M (2005) Isoflurane postconditioning prevents opening of the mitochondrial permeability transition pore through inhibition of glycogen synthase kinase 3β. ASA 103(5):987–995. https://doi.org/10.1097/00000542-200511000-00013
Fu H, Xu H, Chen H, Li Y, Li W, Zhu Q, Zhang Q, Yuan H, Liu F, Wang Q, Miao M (2014) Inhibition of glycogen synthase kinase 3 ameliorates liver ischemia/reperfusion injury via an energy-dependent mitochondrial mechanism. J Hepatol 61(4):816–824. https://doi.org/10.1016/j.jhep.2014.05.017
Fu J, Sun H, Wei H, Dong M, Zhang Y, Xu W, Fang Y, Zhao J (2020) Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats. J Orthop Surg Res 15(1):1–1. https://doi.org/10.1186/s13018-020-01790-8
Garg C, Kaur A, Singh TG, Sharma VK, Singh SK (2022) Therapeutic implications of sonic hedgehog pathway in metabolic disorders: novel target for effective treatment. Pharmacol Res 179:106194. https://doi.org/10.1016/j.phrs.2022.106194
Gerace E, Scartabelli T, Pellegrini-Giampietro DE, Landucci E (2020) Tolerance induced by (S)-3, 5-dihydroxyphenylglycine postconditioning is mediated by the PI3K/Akt/GSK3β signalling pathway in an in vitro model of cerebral ischemia. Neuroscience 433:221–229. https://doi.org/10.1016/j.neuroscience.2019.12.047
Ghali GZ, Ghali MG (2020) Nafamostat mesylate attenuates the pathophysiologic sequelae of neurovascular ischemia. Neural Regen Res 15(12):2217. https://doi.org/10.4103/1673-5374.284981
Girnar GA, Mahajan HS (2021) Cerebral ischemic stroke and different approaches for treatment of stroke. Future J Pharm Sci 7:1. https://doi.org/10.1186/s43094-021-00289-1
Grewal AK, Singh N, Singh TG (2019a) Neuroprotective effect of pharmacological postconditioning on cerebral ischaemia–reperfusion-induced injury in mice. J Pharm Pharmacol 71(6):956–970. https://doi.org/10.1111/jphp.13073
Grewal AK, Singh N, Singh TG (2019b) Effects of resveratrol postconditioning on cerebral ischemia in mice: role of the sirtuin-1 pathway. Can J Physiol Pharmacol 97(11):1094–1101. https://doi.org/10.1139/cjpp-2019-0188
Gu L, Tao Y, Chen C, Ye Y, Xiong X, Sun Y (2018) Initiation of the inflammatory response after renal ischemia/reperfusion injury during renal transplantation. Int Urol Nephrol 50:2027–2035. https://doi.org/10.3390/biomedicines9030306
Gubernatorova EO, Perez-Chanona E, Koroleva EP, Jobin C, Tumanov AV (2016) Murine model of intestinal ischemia-reperfusion injury. J vis Exp 11(111):e53881. https://doi.org/10.3791/53881
Gui B, Hua F, Chen J, Xu Z, Sun H, Qian Y (2014) Protective effects of pretreatment with oleanolic acid in rats in the acute phase of hepatic ischemia-reperfusion injury: role of the PI3K/Akt pathway. Mediators Inflamm. https://doi.org/10.1155/2014/451826
Guo Y, Gupte M, Umbarkar P, Singh AP, Sui JY, Force T, Lal H (2017) Entanglement of GSK-3β, β-catenin and TGF-β1 signaling network to regulate myocardial fibrosis. J Mol Cell Cardiol 110:109–120. https://doi.org/10.1016/j.yjmcc.2017.07.011
Gupta A, Khan H, Kaur A, Singh TG (2021) Novel targets explored in the treatment of alcohol withdrawal syndrome. CNS Neurol Disord Drug Targets 20(2):158–173. https://doi.org/10.2174/1871527319999201118155721
Hausenloy DJ, Yellon DM (2013) Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Investig 123(1):92–100. https://doi.org/10.1172/JCI62874
Heusch G (2020) Myocardial ischaemia–reperfusion injury and cardioprotection in perspective. Nat Rev Cardiol 17(12):773–789. https://doi.org/10.1038/s41569-020-0403-y
Hong YA, Yang KJ, Jung SY, Park KC, Choi H, Oh JM, Lee SJ, Chang YK, Park CW, Yang CW, Kim SY (2017) Paricalcitol pretreatment attenuates renal ischemia-reperfusion injury via prostaglandin E2 receptor EP4 pathway. Oxid Med Cell Longev. https://doi.org/10.1155/2017/5031926
Ihara M, Asanuma H, Yamazaki S, Kato H, Asano Y, Shinozaki Y, Mori H, Minamino T, Asakura M, Sugimachi M, Mochizuki N (2015) An interaction between glucagon-like peptide-1 and adenosine contributes to cardioprotection of a dipeptidyl peptidase 4 inhibitor from myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 308(10):H1287–H1297. https://doi.org/10.1152/ajpheart.00835.2014
Jacobs KM, Bhave SR, Ferraro DJ, Jaboin JJ, Hallahan DE, Thotala D (2012) GSK-3β: a bifunctional role in cell death pathways. Int J Cell Biol. https://doi.org/10.1155/2012/930710
Jeong CW, Yoo KY, Lee SH, Jeong HJ, Lee CS, Kim SJ (2012) Curcumin protects against regional myocardial ischemia/reperfusion injury through activation of RISK/GSK-3β and inhibition of p38 MAPK and JNK. J Cardiovasc Pharmacol Ther 17(4):387–394. https://doi.org/10.1177/1074248412438102
Ji H, Shen XD, Zhang Y, Gao F, Huang CY, Chang WW, Lee C, Ke B, Busuttil RW, Kupiec-Weglinski JW (2012) Activation of cyclic adenosine monophosphate–dependent protein kinase a signaling prevents liver ischemia/reperfusion injury in mice. Liver Transplant 18(6):659–670. https://doi.org/10.1002/lt.23399
Kalogeris T, Baines CP, Krenz M, Korthuis RJ (2012) Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 298:229–317. https://doi.org/10.1016/B978-0-12-394309-5.00006-7
Kamada N, Kanaya N, Hirata N, Kimura S, Namiki A (2008) Cardioprotective effects of propofol in isolated ischemia-reperfused guinea pig hearts: role of KATP channels and GSK-3β. Can J Anaesth 55(9):595–605
Khakha N, Khan H, Kaur A, Singh TG (2023) Therapeutic implications of phosphorylation-and dephosphorylation-dependent factors of cAMP-response element-binding protein (CREB) in neurodegeneration. Pharmacol Rep 1–4. https://doi.org/10.1007/s43440-023-00526-9
Khan H, Kashyap A, Kaur A, Singh TG (2020) Pharmacological postconditioning: a molecular aspect in ischemic injury. J Pharm Pharmacol 72(11):1513–1527. https://doi.org/10.1111/jphp.13336
Khan H, Grewal AK, Singh TG (2022) Pharmacological postconditioning by protocatechuic acid attenuates brain injury in ischemia-reperfusion (I/R) mice model: implications of nuclear factor erythroid-2-related factor pathway. Neuroscience 491:23–31. https://doi.org/10.1016/j.neuroscience.2022.03.016
Khan SS, Janrao S, Srivastava S, Singh SB, Vora L, Khatri DK (2023) GSK-3β: an exuberating neuroinflammatory mediator in Parkinson’s disease. Biochem Pharmacol 11:115496. https://doi.org/10.1016/j.bcp.2023.115496
Kim HJ, Joe Y, Kong JS, Jeong SO, Cho GJ, Ryter SW, Chung HT (2013) Carbon monoxide protects against hepatic ischemia/reperfusion injury via ROS-dependent Akt signaling and inhibition of glycogen synthase kinase 3β. Oxid Med Cell Longev. https://doi.org/10.1155/2013/306421
Kukreja V, Dhiman P (2020) A deep neural network based disease detection scheme for Citrus fruits. In 2020 International conference on smart electronics and communication (ICOSEC) 97–101. IEEE. https://doi.org/10.1109/ICOSEC49089.2020.9215359
Lal H, Zhou J, Ahmad F, Zaka R, Vagnozzi RJ, DeCaul M, Woodgett J, Gao E, Force T (2012) Glycogen synthase kinase-3α limits ischemic injury, cardiac rupture, post–myocardial infarction remodeling and death. Circulation 125(1):65–75. https://doi.org/10.1161/CIRCULATIONAHA.111.050666
Lee JY, Jhun BS, Oh YT, Lee JH, Choe W, Baik HH, Ha J, Yoon KS, Kim SS, Kang I (2006) Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-α production through inhibition of PI 3-kinase/Akt and NF-κB activation in murine BV2 microglial cells. Neurosci Lett 396(1):1–6. https://doi.org/10.1016/j.neulet.2005.11.004
Li HJ, Yin H, Yao YY, Shen B, Bader M, Chao L, Chao J (2007) Tissue kallikrein protects against pressure overload-induced cardiac hypertrophy through kinin B2 receptor and glycogen synthase kinase-3β activation. Cardiovasc Res 73(1):130–142. https://doi.org/10.1016/j.cardiores.2006.10.014
Lin D, Wang L, Yan S, Zhang Q, Zhang JH, Shao A (2019) The role of oxidative stress in common risk factors and mechanisms of cardio-cerebrovascular ischemia and depression. Oxid Med Cell Longev. https://doi.org/10.1155/2019/2491927
Liu H, Wu X, Luo J, Zhao L, Li X, Guo H, Bai H, Cui W, Guo W, Feng D, Qu Y (2020a) Adiponectin peptide alleviates oxidative stress and NLRP3 inflammasome activation after cerebral ischemia-reperfusion injury by regulating AMPK/GSK-3β. Exp Neurol 329:113302. https://doi.org/10.1016/j.expneurol.2020.113302
Liu G, Zhang BF, Hu Q, Liu XP, Chen J (2020b) Syringic acid mitigates myocardial ischemia reperfusion injury by activating the PI3K/Akt/GSK-3β signaling pathway. Biochem Biophys Res Commun 531(2):242–249. https://doi.org/10.1016/j.bbrc.2020.07.047
Loberg RD, Vesely E, Brosius FC (2022) Enhanced glycogen synthase kinase-3β activity mediates hypoxia-induced apoptosis of vascular smooth muscle cells and is prevented by glucose transport and metabolism. J Biol Chem 277(44):41667–41673. https://doi.org/10.1074/jbc.M206405200
Loizzo D, di Meo NA, Peluso MR, Rutigliano M, Matera M, Miacola C, Palella G, Tedeschi M, Spilotros M, Ferro M, Tătaru OS (2021) Novel insights into the molecular mechanisms of ischemia/reperfusion injury in kidney transplantation. Transplantology 2(2):191–207. https://doi.org/10.3390/transplantology2020018
Luo X, Cai H, Ni J, Bhindi R, Lowe HC, Chesterman CN, Khachigian LM (2009) c-Jun DNAzymes inhibit myocardial inflammation, ROS generation, infarct size, and improve cardiac function after ischemia-reperfusion injury. Arterioscler Thromb Vasc Biol 29(11):1836–1842. https://doi.org/10.1161/ATVBAHA.109.189753
Ma J, Zhang XL, Wang CY, Lin Z, Tao JR, Liu HC (2015) Dexmedetomidine alleviates the spinal cord ischemia-reperfusion injury through blocking mast cell degranulation. Int J Clin Exp Med 8(9):14741. PMCID: PMC4658845
Mao ZJ, Lin H, Hou JW, Zhou Q, Wang Q, Chen YH (2019) A meta-analysis of resveratrol protects against myocardial ischemia/reperfusion injury: evidence from small animal studies and insight into molecular mechanisms. Oxid Med Cell Longev. https://doi.org/10.1155/2019/5793867
McCubrey JA, Lertpiriyapong K, Steelman LS, Abrams SL, Cocco L, Ratti S, Martelli AM, Candido S, Libra M, Montalto G, Cervello M (2017) Regulation of GSK-3 activity by curcumin, berberine and resveratrol: potential effects on multiple diseases. Adv Biol Regul 65:77–88. https://doi.org/10.1016/j.jbior.2017.05.005
Mozaffari MS, Liu JY, Abebe W, Baban B (2013) Mechanisms of load dependency of myocardial ischemia reperfusion injury. American journal of cardiovascular disease. Am J Cardiovasc 3(4):180 PMCID: PMC3819580
Nandan MO, Yang VW (2009) The role of Krüppel-like factors in the reprogramming of somatic cells to induced pluripotent stem cells. Histol Histopathol. https://doi.org/10.14670/hh-24.1343
Park SA, Lee JW, Herbst RS, Koo JS (2016) GSK-3α is a novel target of CREB and CREB-GSK-3α signaling participates in cell viability in lung cancer. PLoS ONE 11(4):e0153075. https://doi.org/10.1371/journal.pone.0153075
Park DJ, Kang JB, Shah FA, Koh PO (2019) Resveratrol modulates the Akt/GSK-3β signaling pathway in a middle cerebral artery occlusion animal model. Lab Anim Res 35(1):1–8. https://doi.org/10.1186/s42826-019-0019-8
Parlakpinar H, Orum MH, Sagir M (2013) Pathophysiology of myocardial ischemia reperfusion injury: a review. Med Sci 2(4):935–954. https://doi.org/10.1155/2015/864946
Pires EN, Frozza RL, Hoppe JB, de Melo MB, Salbego CG (2014) Berberine was neuroprotective against an in vitro model of brain ischemia: survival and apoptosis pathways involved. Brain Res 1557:26–33. https://doi.org/10.1016/j.brainres.2014.02.021
Rahman S, Li J, Bopassa JC, Umar S, Iorga A, Partownavid P, Eghbali M (2011) Phosphorylation of GSK-3β mediates intralipid-induced cardioprotection against ischemia/reperfusion injury. ASA 115(2):242–253. https://doi.org/10.1097/ALN.0b013e318223b8b9
Ramagiri S, Taliyan R (2017) Remote limb ischemic post conditioning during early reperfusion alleviates cerebral ischemic reperfusion injury via GSK-3β/CREB/BDNF pathway. Eur J Pharmacol 803:84–93. https://doi.org/10.1016/j.ejphar.2017.03.028
Rehni AK, Singh TG, Bhateja P, Singh N, Arora S (2010) Involvement of cyclic adenosine diphosphoribose receptor activation in ischemic preconditioning induced protection in mouse brain. Brain Res 1309:75–82. https://doi.org/10.1016/j.brainres.2009.10.071
Rihal V, Khan H, Kaur A, Singh TG (2022) Vitamin D as therapeutic modulator in cerebrovascular diseases: a mechanistic perspectives. Crit Rev Food Sci Nutr 1–23. https://doi.org/10.1080/10408398.2022.2050349
Rossi M, Korpak K, Doerfler A, Zouaoui Boudjeltia K (2021) Deciphering the role of heme oxygenase-1 (Ho-1) expressing macrophages in renal ischemia-reperfusion injury. Biomedicines 9(3):306. https://doi.org/10.3390/biomedicines9030306
Saklani P, Khan H, Gupta S, Kaur A, Singh TG (2022) Neuropeptides: potential neuroprotective agents in ischemic injury. Life Sci 288:120186. https://doi.org/10.1016/j.lfs.2021.120186
Salvadori M, Rosso G, Bertoni E (2015) Update on ischemia-reperfusion injury in kidney transplantation: pathogenesis and treatment. World J Transplant 5(2):52. https://doi.org/10.5500/wjt.v5.i2.52
Sankhyan A, Pawar PK (2013) Metformin loaded non-ionic surfactant vesicles: optimization of formulation, effect of process variables and characterization. DARU J Pharm Sci 21:1–8. https://doi.org/10.1186/2008-2231-21-7
Seok S, Fu T, Choi SE, Li Y, Zhu R, Kumar S, Sun X, Yoon G, Kang Y, Zhong W, Ma J (2014) Transcriptional regulation of autophagy by an FXR–CREB axis. Nature 516(7529):108–111. https://doi.org/10.1038/nature13949
Shao M, Zheng C, Ma X, Lyu F (2021) Ecto-5’-nucleotidase (CD73) inhibits dorsal root ganglion neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway. Exp Ther Med 22(6):1–9. https://doi.org/10.3892/etm.2021.10809
Sharma VK, Singh TG (2020) CREB: a multifaceted target for Alzheimer’s disease. Curr Alzheimer Res 17(14):1280–1293. https://doi.org/10.2174/1567205018666210218152253
Sharma AK, Thanikachalam PV, Bhatia S (2020a) The signaling interplay of GSK-3β in myocardial disorders. Drug Discov Today 25(4):633–641. https://doi.org/10.1016/j.drudis.2020.01.017
Sharma VK, Singh TG, Singh S (2020b) Cyclic nucleotides signaling and phosphodiesterase inhibition: defying Alzheimer’s disease. Curr Drug Targets 21(13):1371–1384. https://doi.org/10.2174/1389450121666200727104728
Sharma A, Khan H, Singh TG, Grewal AK, Najda A, Kawecka-Radomska M, Kamel M, Altyar AE, Abdel-Daim MM (2021) Pharmacological modulation of ubiquitin-proteasome pathways in oncogenic signaling. Int J Mol Sci 22(21):11971. https://doi.org/10.3390/ijms222111971
Simao F, Matte A, Pagnussat AS, Netto CA, Salbego CG (2012) Resveratrol prevents CA1 neurons against ischemic injury by parallel modulation of both GSK-3β and CREB through PI3-K/Akt pathways. Eur J Neurosci 36(7):2899–2905. https://doi.org/10.1111/j.1460-9568.2012.08229.x
Singh S, Singh TG (2020) Role of nuclear factor kappa B (NF-κB) signalling in neurodegenerative diseases: an mechanistic approach. Curr Neuropharmacol 18(10):918–935. https://doi.org/10.2174/1570159X18666200207120949
Singh SP, Tao S, Fields TA, Webb S, Harris RC, Rao R (2015) Glycogen synthase kinase-3 inhibition attenuates fibroblast activation and development of fibrosis following renal ischemia-reperfusion in mice. Dis Model Mech 8(8):931–940. https://doi.org/10.1242/dmm.020511
Smith SF, Hosgood SA, Nicholson ML (2019) Ischemia-reperfusion injury in renal transplantation: 3 key signaling pathways in tubular epithelial cells. Kidney Int 95(1):50–56. https://doi.org/10.1016/j.kint.2018.10.009
Soares RO, Losada DM, Jordani MC, Évora P, Castro-e-Silva O (2019) Ischemia/reperfusion injury revisited: an overview of the latest pharmacological strategies. Int J Mol Sci 20(20):5034. https://doi.org/10.3390/ijms20205034
Su M, Ren S, Zhong W, Han X (2017) Impact of propofol on renal ischemia/reperfusion endoplasmic reticulum stress. Acta Cir Bras 32:533–539. https://doi.org/10.1590/s0102-865020170070000004
Su S, Zhang P, Zhang Q, Yin Z (2019) GSK-3β inhibitor induces expression of the TLR4/MyD88/NF-κB signaling pathway to protect against renal ischemia-reperfusion injury during rat kidney transplantation. Inflammation 42:2105–2118. https://doi.org/10.1007/s10753-019-01074-2
Tsutsui S, Schnermann J, Noorbakhsh F, Henry S, Yong VW, Winston BW, Warren K, Power C (2004) A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis. J Neurosci 24(6):1521–1529. https://doi.org/10.1523/JNEUROSCI.4271-03.2004
Vasileva AK, Plotnikov EY, Kazachenko AV, Kirpatovsky VI, Zorov DB (2010) Inhibition of GSK-3β decreases the ischemia-induced death of renal cells. Bull Exp Biol Med 149:303–307. https://doi.org/10.1007/s10517-010-0932-1
Wong YL, Lautenschläger I, Hummitzsch L, Zitta K, Cossais F, Wedel T, Rusch R, Berndt R, Gruenewald M, Weiler N, Steinfath M (2021) Effects of different ischemic preconditioning strategies on physiological and cellular mechanisms of intestinal ischemia/reperfusion injury: implication from an isolated perfused rat small intestine model. PLoS ONE 16(9):e0256957. https://doi.org/10.1371/journal.pone.0256957
Wu MY, Yiang GT, Liao WT, Tsai AP, Cheng YL, Cheng PW, Li CY, Li CJ (2018) Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol Biochem 46(4):1650–1667. https://doi.org/10.1159/000489241
Wu L, Fang J, Yuan X, Xiong C, Chen L (2019) Adropin reduces hypoxia/reoxygenation-induced myocardial injury via the reperfusion injury salvage kinase pathway. Exp Ther Med 18(5):3307–3314. https://doi.org/10.3892/etm.2019.7937
Wu X, Liang Y, Jing X, Lin D, Chen Y, Zhou T, Peng S, Zheng D, Zeng Z, Lei M, Huang K (2018b) Rifampicin prevents SH-SY5Y cells from rotenone-induced apoptosis via the PI3K/Akt/GSK-3β/CREB signaling pathway. Neurochem Res 886–93. https://doi.org/10.1007/s11064-018-2494-y
Xia Y, Rao J, Yao A, Zhang F, Li G, Wang X, Lu L (2012) Lithium exacerbates hepatic ischemia/reperfusion injury by inhibiting GSK-3β/NF-κB-mediated protective signaling in mice. Eur J Pharmacol 697(1–3):117–125. https://doi.org/10.1016/j.ejphar.2012.09.009
Xie LH, Gwathmey JK, Zhao Z (2021) Cardiac adaptation and cardioprotection against arrhythmias and ischemia-reperfusion injury in mammalian hibernators. Pflug Arch Eur J Physiol 473:407–416. https://doi.org/10.1007/s00424-020-02511-0
Xue Z, Zhang Y, Liu Y, Zhang C, Gao F, Busuttil RW, Zheng S, Kupiec-Weglinski JW, Ji H (2020) PACAP neuropeptide promotes hepatocellular protection via CREB-KLF4 dependent autophagy in mouse liver ischemia reperfusion injury. Theranostics 10(10):4453. https://doi.org/10.7150/thno.42354
Yang S, Li H, Tang L, Ge G, Ma J, Qiao Z, Liu H, Fang W (2015) Apelin-13 protects the heart against ischemia-reperfusion injury through the RISK-GSK-3β-mPTP pathway. Arch Med Sci 11(5):1065–1073. https://doi.org/10.5114/aoms.2015.54863
Yang L, Chen X, Bi Z, Liao J, Zhao W, Huang W (2021) Curcumin attenuates renal ischemia reperfusion injury via JNK pathway with the involvement of p300/CBP-mediated histone acetylation. Korean J Physiol Pharmacol 25(5):413–423. https://doi.org/10.4196/kjpp.2021.25.5.413
Yao Y, Wang L, Jin P, Li N, Meng Y, Wang C, Xu M, Zhang Y, Bian J, Deng X (2017) Methane alleviates carbon tetrachloride induced liver injury in mice: anti-inflammatory action demonstrated by increased PI3K/Akt/GSK-3β-mediated IL-10 expression. J Mol Histol 48:301–310. https://doi.org/10.1007/s10735-017-9728-1
Ye Z, Chen O, Zhang R, Nakao A, Fan D, Zhang T, Gu Z, Tao H, Sun X (2015) Methane attenuates hepatic ischemia/reperfusion injury in rats through antiapoptotic, anti-inflammatory, and antioxidative actions. Shock 44(2):181–187. https://doi.org/10.1097/SHK.0000000000000385
Yune TY, Park HG, Lee JY, Oh TH (2008) Estrogen-induced Bcl-2 expression after spinal cord injury is mediated through phosphoinositide-3-kinase/Akt-dependent CREB activation. J Neurotrauma 25(9):1121–1131. https://doi.org/10.1089/neu.2008.0544
Zakharova NM, Tarahovsky YS, Fadeeva IS, Komelina NP, Khrenov MO, Glushkova OV, Prokhorov DA, Kutyshenko VP, Kovtun AL (2019) A pharmacological composition for induction of a reversible torpor-like state and hypothermia in rats. Life Sci 219:190–198. https://doi.org/10.1016/j.lfs.2019.01.023
Zhang X, Zhang X, Wang C, Li Y, Dong L, Cui L, Wang L, Liu Z, Qiao H, Zhu C, Xing Y (2012) Neuroprotection of early and short-time applying berberine in the acute phase of cerebral ischemia: up-regulated pAkt, pGSK and pCREB, down-regulated NF-κB expression, ameliorated BBB permeability. Brain Res 1459:61–70. https://doi.org/10.1016/j.brainres.2012.03.065
Zhang F, Ru N, Shang ZH, Chen JF, Yan C, Li Y, Liang J (2017) Daidzein ameliorates spinal cord ischemia/reperfusion injury-induced neurological function deficits in Sprague-Dawley rats through PI3K/Akt signaling pathway. Exp Ther Med 14(5):4878–4886. https://doi.org/10.3892/etm.2017.5166
Zhang X, Du Q, Yang Y, Wang J, Liu Y, Zhao Z, Zhu Y, Liu C (2018) Salidroside alleviates ischemic brain injury in mice with ischemic stroke through regulating BDNK mediated PI3K/Akt pathway. Biochem Pharmacol 156:99–108. https://doi.org/10.1016/j.bcp.2018.08.015
Zhao G, Shen X, Zhu Y, Wang Q, Lyu Y (2017) Effect of propofol pretreatment against hepatic ischemia-reperfusion injury on mitochondrial permeability transition pore in rats. Chin J Hepatobiliary Surg 468–73. https://doi.org/10.1155/2017/2186383
Zhu T, Wang L, Xie W, Meng X, Feng Y, Sun G, Sun X (2021) Notoginsenoside R1 improves cerebral ischemia/reperfusion injury by promoting neurogenesis via the BDNF/Akt/CREB pathway. Front Pharmacol 12:615998. https://doi.org/10.3389/fphar.2021.615998
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The authors are grateful to the Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, Punjab, India, for providing the necessary facilities to carry out the research work.
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Conceptualization: Conceived- and designed the experiments: Thakur Gurjeet Singh. Analyzed the data: Amarjot Kaur. Wrote the manuscript: Heena Khan, Annu Bangar Visualization: Amarjot Kaur, Thakur Gurjeet Singh Editing of the Manuscript: Heena khan, Thakur Gurjeet Singh Critically reviewed the article: Thakur Gurjeet Singh Supervision: Thakur Gurjeet Singh.
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Khan, H., Bangar, A., Grewal, A.K. et al. Mechanistic Implications of GSK and CREB Crosstalk in Ischemia Injury. Neurotox Res 42, 1 (2024). https://doi.org/10.1007/s12640-023-00680-1
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DOI: https://doi.org/10.1007/s12640-023-00680-1