硫化通过抑制内质网膜应激减轻血管光滑肌细胞衰老
Lijie Jiao1, Qiuyi Yan1, Jiahe Yang1
1Institute of Cardiovascular Diseases, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361006, Fujian, China; School of Medicine, Xiamen University, Xiamen 361102, Fujian, China.
硫化 (H2S) 通过减少内质网膜 (ER) 压力,延缓了血管光滑肌细胞 (VSMC) 的衰老. 这涉及向下调节关键的ER应力路径和增强GRP78的S-硫化.
科学领域:
- 心血管生物学
- 细胞衰老
- 分子医学
背景情况:
- 血管光滑肌细胞衰老有助于血管功能障碍和心血管疾病.
- 内质网膜 (ER) 的压力与VSMC衰老有关,但硫化 (H2S) 的作用尚不清楚.
研究的目的:
- 调查H2S是否可以抑制ER压力以缓解VSMC衰老.
- 阐明H2S对VSMC衰老的影响的分子机制.
主要方法:
- 使用D-银来诱导VSMC衰老和氧化应激的细胞实验.
- 用H2S处理和ER压力标志物的分析,VSMC衰老指标,以及相关的信号通路.
- 在自然衰老的小鼠中进行实验,以验证体内发现.
- 研究GRP78S-硫化和Cys42位点在H2S的影响中的作用.
主要成果:
- D- 银糖诱导了VSMC衰老,氧化应激和ER应激,同时降低了H2S的产生.
- 在实验室中,H2S补充剂逆转了D- 银引起的这些影响,并缓解了小鼠的血管衰老表型.
- H2S在Cys42部位恢复了GRP78的S-硫化,并且它的击倒或突变取消了H2S的保护作用.
结论:
- 通过减轻ER压力,H2S延迟了VSMC衰老.
- 这通过IRE1-XBP1,PERK-eIF-2α-ATF4和ATF6通路的下调发生.
- H2S通过增加Cys42位点的GRP78 S-硫化作用来发挥其保护作用.
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