Sodium butyrate attenuates rotenone-induced toxicity by activation of autophagy through epigenetically regulating PGC-1α expression in PC12 cells
Sodium butyrate attenuates rotenone-induced toxicity by activation of autophagy through epigenetically regulating PGC-1α expression in PC12 cells
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丁酸钠通过表观遗传调节 PC12 细胞中 PGC-1α 的表达来激活自噬，从而减轻鱼藤酮诱导的毒性
DOI：
10.1016/j.brainres.2021.147749
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发表时间：
2021-12
期刊：
影响因子：
2.9
通讯作者：
Qin Xiao
中科院分区：
文献类型：
--
作者：
Yi Zhang;Shaoqing Xu;Yiwei Qian;Xiaoqin He;Chengjun Mo;Xiaodong Yang;Qin Xiao
短链脂肪酸（SCFAs）被认为是肠道微生物群与帕金森病（PD）发病机制之间的关键分子链接。然而，SCFAs在PD发病机制中的作用仍存在争议。自噬对α-突触核蛋白的降解具有重要作用，而α-突触核蛋白的降解对PD的发生至关重要。然而，SCFAs是否可以调节PD的自噬仍然未知。我们的目的是研究短链脂肪酸在鱼藤酮处理大鼠多巴胺能PC12细胞中的作用，并探讨其潜在机制。Western blot检测细胞中α-突触核蛋白、过氧化物酶体增殖物激活受体γ共激活因子-1α (PGC-1α)和微管相关蛋白1轻链3 β (LC3B)-II的表达水平。采用染色质免疫沉淀-定量聚合酶链反应（ChIP-qPCR）检测pgc -1α启动子区组蛋白乙酰化水平。在三种scfa中，丁酸钠（NaB）对鱼藤酮诱导的毒性具有保护作用。NaB通过激活自噬通路，降低鱼藤酮诱导的α-突触核蛋白的表达。值得注意的是，NaB通过上调PGC-1α表达激活自噬途径。更重要的是，NaB提高了PGC-1α启动子区域组蛋白3赖氨酸9乙酰化（H3K9Ac）和组蛋白3赖氨酸27乙酰化（H3K27Ac）水平，表明NaB通过组蛋白乙酰化修饰促进PGC-1α表达。综上所述，NaB可能通过表观遗传修饰上调PGC-1α的表达，激活鱼藤酮诱导的自噬通路，从而起到保护鱼藤酮毒性的作用。
Short-chain fatty acids (SCFAs) are considered the key molecular link between gut microbiota and pathogenesis of Parkinson’s disease (PD). However, the role of SCFAs in PD pathogenesis is controversial. Autophagy is important for the degradation of α-synuclein, which is critical to the development of PD. However, whether SCFAs can regulate autophagy in PD remains unknown. We aimed to investigate the role of SCFAs and explore the potential mechanisms in rat dopaminergic PC12 cells treated with rotenone. Expression levels of α-synuclein, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and microtubule-associated protein 1 light chain 3 beta (LC3B)-II were detected by Western blot. Histone acetylation levels atPGC-1αpromoter region were measured using chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). Among the three SCFAs, sodium butyrate (NaB) protected against rotenone-induced toxicity. NaB activated autophagy pathway and reduced rotenone-induced α-synuclein expression through the activation of autophagy. Notably, NaB activated autophagy pathway through upregulating PGC-1α expression. More importantly, NaB promoted the levels of histone 3 lysine 9 acetylation (H3K9Ac) and histone 3 lysine 27 acetylation (H3K27Ac) atPGC-1αpromoter region, indicating that NaB promotes PGC-1α expression via histone acetylation modification. In conclusion, NaB can protect against rotenone-induced toxicity through activation of the autophagy pathway by upregulating PGC-1α expression via epigenetic modification.
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肠道微生物群形成短链脂肪酸及其对人代谢的影响。
影响因子：
12.2
作者：
Morrison DJ;Preston T
通讯作者：
Preston T
DOI：
10.1042/bss0660085
发表时间：
1999-01-01
期刊：
MITOCHONDRIA AND CELL DEATH
影响因子：
--
作者：
Greenamyre, JT;MacKenzie, G;Stephans, SE
通讯作者：
Stephans, SE
影响因子：
15.1
作者：
Qian, Yiwei;Yang, Xiaodong;Xiao, Qin
通讯作者：
Xiao, Qin
影响因子：
4.4
作者：
Liu, Jiaming;Wang, Fangyan;Sun, Jing
通讯作者：
Sun, Jing
DOI：
10.1073/pnas.75.5.2239
发表时间：
1978-05
影响因子：
11.1
作者：
G. Vidali;L. Boffa;E. Bradbury;V. Allfrey
通讯作者：
G. Vidali;L. Boffa;E. Bradbury;V. Allfrey