The neurotrophin nerve growth factor (NGF) and its precursor proNGF are both bioactive and exert similar or opposite actions depending on the cell target and its milieu. The balance between NGF and proNGF is crucial for cell and tissue homeostasis and it is considered an indicator of pathological conditions. Proteolytical cleavage of proNGF to the mature form results in different fragments, whose function and/or bioactivity is still unclear. The present study was conducted to investigate the distribution of proNGF fragments derived from endogenous cleavage in brain and peripheral tissues of adult rats in the healthy condition and following inflammatory lipopolysaccharide (LPS) challenge. Different anti-proNGF antibodies were tested and the presence of short peptides corresponding to the prodomain sequence (pdNGFpep) was identified. Processing of proNGF was found to be tissue-specific and accumulation of pdNGFpeps was found in inflamed tissues, mainly in testis, intestine and heart, suggesting a possible correlation between organ functions and a response to insults and/or injury. The bioactivity of pdNGFpep was also demonstrated in vitro by using primary hippocampal neurons. Our study supports a biological function for the NGF precursor prodomain and indicates that short peptides from residues 1–60, differing from the 70–110 sequence, induce apoptosis, thereby opening the way for identification of new molecular targets to study pathological conditions.

中文翻译：

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成年大鼠组织中 ProNGF 的加工和 NGF 前结构域肽的生物活性

神经营养蛋白神经生长因子 (NGF) 及其前体 proNGF 均具有生物活性，并根据细胞靶标及其环境发挥相似或相反的作用。 NGF 和 proNGF 之间的平衡对于细胞和组织稳态至关重要，被认为是病理状况的指标。 proNGF 蛋白水解为成熟形式会产生不同的片段，其功能和/或生物活性仍不清楚。本研究旨在调查健康状况下和炎性脂多糖（LPS）攻击后成年大鼠脑和外周组织中内源性裂解衍生的 proNGF 片段的分布。测试了不同的抗 proNGF 抗体，并鉴定了对应于前结构域序列 (pdNGFpep) 的短肽的存在。研究发现 proNGF 的加工具有组织特异性，并且在发炎组织（主要是睾丸、肠和心脏）中发现了 pdNGFpeps 的积累，这表明器官功能与对侮辱和/或损伤的反应之间可能存在相关性。 pdNGFpep 的生物活性也在体外通过使用原代海马神经元得到了证明。我们的研究支持 NGF 前体前结构域的生物学功能，并表明残基 1-60 的短肽（与 70-110 序列不同）可诱导细胞凋亡，从而为鉴定新分子靶点以研究病理状况开辟了道路。