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Reactive Halogen Species: Role in Living Systems and Current Research Approaches

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Abstract

Reactive halogen species (RHS) are highly reactive compounds that are normally required for regulation of immune response, inflammatory reactions, enzyme function, etc. At the same time, hyperproduction of highly reactive compounds leads to the development of various socially significant diseases – asthma, pulmonary hypertension, oncological and neurodegenerative diseases, retinopathy, and many others. The main sources of (pseudo)hypohalous acids are enzymes from the family of heme peroxidases – myeloperoxidase, lactoperoxidase, eosinophil peroxidase, and thyroid peroxidase. Main targets of these compounds are proteins and peptides, primarily methionine and cysteine residues. Due to the short lifetime, detection of RHS can be difficult. The most common approach is detection of myeloperoxidase, which is thought to reflect the amount of RHS produced, but these methods are indirect, and the results are often contradictory. The most promising approaches seem to be those that provide direct registration of highly reactive compounds themselves or products of their interaction with components of living cells, such as fluorescent dyes. However, even such methods have a number of limitations and can often be applied mainly for in vitro studies with cell culture. Detection of reactive halogen species in living organisms in real time is a particularly acute issue. The present review is devoted to RHS, their characteristics, chemical properties, peculiarities of interaction with components of living cells, and methods of their detection in living systems. Special attention is paid to the genetically encoded tools, which have been introduced recently and allow avoiding a number of difficulties when working with living systems.

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Abbreviations

EPO:

eosinophil peroxidase

ESIPT:

excited state intramolecular proton transfer

FRET:

Förster resonance energy transfer

GFP:

green fluorescent protein

Hal– :

halides

HOSCN:

hypothiocyanous acid

ICT:

intramolecular charge transfer

LDL:

low-density lipoproteins

LPO:

lactoperoxidase

MPO:

myeloperoxidase

PET:

positron emission tomography

PeT:

photo-induced electron transfer

Pxdn:

peroxidasin

RHS:

reactive halogen species

SCN– :

thiocyanate ion

TBET:

nonradiative through-bond energy transfer

TPO:

thyroid peroxidase

YFP:

yellow fluorescent protein

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Funding

This work was financially supported by the Russian Science Foundation, grants nos. 20-15-00390 (chapters “Introduction” and “Main Types of Biologically Significant Reactive Halogen Species: HOCl, HOBr, HOSCN”) and 22-15-00299 (chapters “Approaches to Investigation of Reactive Halogen Species” and “Classification of Synthetic Fluorescent Indicators of Reactive Halogen Species”).

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Authors and Affiliations

  1. Faculty of Biology, Lomonosov Moscow State University, 119234, Moscow, Russia

    Yuliya V. Khramova, Veronika A. Katrukha & Victoria V. Chebanenko

  2. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia

    Yuliya V. Khramova, Veronika A. Katrukha, Victoria V. Chebanenko, Alexander I. Kostyuk & Dmitry S. Bilan

  3. Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, 117997, Moscow, Russia

    Alexander I. Kostyuk & Dmitry S. Bilan

  4. Institute of Experimental Medicine, 197022, Saint-Petersburg, Russia

    Nikolay P. Gorbunov & Alexey V. Sokolov

  5. Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, 119435, Moscow, Russia

    Oleg M. Panasenko & Alexey V. Sokolov

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  1. Yuliya V. Khramova
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  2. Veronika A. Katrukha
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  4. Alexander I. Kostyuk
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  5. Nikolay P. Gorbunov
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  8. Dmitry S. Bilan
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Contributions

Y.V.Kh., V.A.K., V.V.Ch., and A.V.K. writing of the sections “Approaches to Investigation of Reactive Halogen Species”, “Classification of Synthetic Fluorescent Indicators of Reactive Halogen Species”, “Conclusions”; N.P.G., O.M.P., and A.V.S. writing of the sections “Introduction” and “Main Types of Biologically Significant Reactive Halogen Species: HOCl, HOBr, HOSCN”; A.V.S. and D.S.B. editing of the text of the article.

Corresponding authors

Correspondence to Yuliya V. Khramova, Alexey V. Sokolov or Dmitry S. Bilan.

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This work does not contain any studies involving human and animal subjects. The authors of this work declare that they have no conflicts of interest.

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Translated from Uspekhi Biologicheskoi Khimii, 2024, Vol. 64, pp. 179-218.

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Khramova, Y.V., Katrukha, V.A., Chebanenko, V.V. et al. Reactive Halogen Species: Role in Living Systems and Current Research Approaches. Biochemistry Moscow 89 (Suppl 1), S90–S111 (2024). https://doi.org/10.1134/S0006297924140062

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