期刊
MOLECULES
卷 26, 期 19, 页码 -出版社
MDPI
DOI: 10.3390/molecules26195883
关键词
2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-b-D-pyranoside; cellular bioenergetics; mitochondrial homeostasis; O-GlcNAcylation; oxygen glucose deprivation/reoxygenation stress; neuroprotection
资金
- National Key Research and Development Program of China [2017YFA0104700]
- National Natural Science Foundation of China [81401094, 81901933]
- Natural Science Research Project of Nantong Science and Technology Bureau [JC2020033]
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
O-GlcNAcylation, as a metabolic sensor, plays an important role in linking metabolism to cellular function. SalA-4g, a salidroside analogue, has been shown to enhance protein O-GlcNAc levels and improve neuronal tolerance to ischemia by regulating mitochondrial homeostasis. Mitochondrial protein O-GlcNAcylation mediated by SalA-4g is critically involved in neuroprotection against ischemic-like conditions.
O-GlcNAcylation is a nutrient-driven post-translational modification known as a metabolic sensor that links metabolism to cellular function. Recent evidences indicate that the activation of O-GlcNAc pathway is a potential pro-survival pathway and that acute enhancement of this response is conducive to the survival of cells and tissues. 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-beta-d-pyranoside (SalA-4g), is a salidroside analogue synthesized in our laboratory by chemical structure-modification, with a phenyl ring containing a para-methoxy group and a sugar ring consisting of N-acetylglucosamine. We have previously shown that SalA-4g elevates levels of protein O-GlcNAc and improves neuronal tolerance to ischemia. However, the specific target of SalA-4g regulating O-GlcNAcylation remains unknown. To address these questions, in this study, we have focused on mitochondrial network homeostasis mediated by O-GlcNAcylation in SalA-4g's neuroprotection in primary cortical neurons under ischemic-like conditions. O-GlcNAc-modified mitochondria induced by SalA-4g demonstrated stronger neuroprotection under oxygen glucose deprivation and reoxygenation stress, including the improvement of mitochondrial homeostasis and bioenergy, and inhibition of mitochondrial apoptosis pathway. Blocking mitochondrial protein O-GlcNAcylation with OSMI-1 disrupted mitochondrial network homeostasis and antagonized the protective effects of SalA-4g. Collectively, these data demonstrate that mitochondrial homeostasis mediated by mitochondrial protein O-GlcNAcylation is critically involved in SalA-4g neuroprotection.
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