IP3R1/GRP75/VDAC1 complex mediates endoplasmic reticulum stress-mitochondrial oxidative stress in diabetic atrial remodeling.
IP3R1/GRP75/VDAC1 complex mediates endoplasmic reticulum stress-mitochondrial oxidative stress in diabetic atrial remodeling.
复制标题
IP3R1/GRP75/VDAC1 复合物介导糖尿病心房重构中的内质网应激-线粒体氧化应激。
DOI：
10.1016/j.redox.2022.102289
复制
发表时间：
2022-06
期刊：
影响因子：
11.4
通讯作者：
Liu T
中科院分区：
文献类型：
--
作者：
Yuan M;Gong M;He J;Xie B;Zhang Z;Meng L;Tse G;Zhao Y;Bao Q;Zhang Y;Yuan M;Liu X;Luo C;Wang F;Li G;Liu T
内质网（ER）应激和线粒体功能障碍是心房重构的重要机制，是2型糖尿病（T2 DM）心房颤动（AF）发生的易感因素。然而，这些过程的分子机制，特别是它们之间的相互作用尚未完全阐明。探讨内质网应激-线粒体氧化应激在糖尿病心房重构和房颤诱发中的作用。以小鼠心房肌细胞（HL-1细胞）和T2 DM大鼠为研究模型。在糖尿病大鼠心房中观察到显著的ER应激。在用衣霉素（TM）（一种ER应激激动剂）处理后，质谱（MS）鉴定了几种已知的ER应激和钙调蛋白蛋白，包括热休克蛋白家族A（HSP 70）成员[HSPA] 5 [GRP 78]）和HSPA 9（GRP 75，葡萄糖调节蛋白75）。原位邻位连接实验表明TM可诱导HL-1细胞IP 3R 1-GRP 75-VDAC 1（inositol 1，4，5-trisphosphate receptor 1-glucose-regulated protein 75-voltage dependent anion channel 1）复合物蛋白表达增加。HL-1细胞中GRP 75的小干扰RNA沉默和小鼠模型中GRP 75的条件性敲除导致从ER到线粒体的钙转运受损，并减轻线粒体氧化应激和钙超载。此外，GRP 75缺陷减弱Myh 6-Cre+/Hspa 9 flox/flox + TM小鼠的心房重构和AF进展。IP 3R 1-GRP 75-VDAC 1复合物介导内质网应激-线粒体氧化应激，在糖尿病心房重构中发挥重要作用。心房颤动相关的内质网应激。GRP 75有助于ER-线粒体串扰。抑制GRP 75减弱糖尿病心房重构。
Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are important mechanisms of atrial remodeling, predisposing to the development of atrial fibrillation (AF) in type 2 diabetes mellitus (T2DM). However, the molecular mechanisms underlying these processes especially their interactions have not been fully elucidated. To explore the potential role of ER stress–mitochondrial oxidative stress in atrial remodeling and AF induction in diabetes. Mouse atrial cardiomyocytes (HL-1 cells) and rats with T2DM were used as study models. Significant ER stress was observed in the diabetic rat atria. After treatment with tunicamycin (TM), an ER stress agonist, mass spectrometry (MS) identified several known ER stress and calmodulin proteins, including heat shock protein family A (HSP70) member [HSPA] 5 [GRP78]) and HSPA9 (GRP75, glucose-regulated protein 75). In situ proximity ligation assay indicated that TM led to increased protein expression of the IP3R1–GRP75–VDAC1 (inositol 1,4,5-trisphosphate receptor 1–glucose-regulated protein 75–voltage-dependent anion channel 1) complex in HL-1 cells. Small interfering RNA silencing of GRP75 in HL-1 cells and GRP75 conditional knockout in a mouse model led to impaired calcium transport from the ER to the mitochondria and alleviated mitochondrial oxidative stress and calcium overload. Moreover, GRP75 deficiency attenuated atrial remodeling and AF progression in Myh6-Cre+/Hspa9flox/flox + TM mice. The IP3R1–GRP75–VDAC1 complex mediates ER stress–mitochondrial oxidative stress and plays an important role in diabetic atrial remodeling. Endoplasmic reticulum stress associated with atrial fibrillation. GRP75 contributes to the ER-mitochondria crosstalk. Inhibition of GRP75 attenuated diabetic atrial remodeling.
登录
查看更多内容
影响因子：
16.6
作者：
Back SH;Kaufman RJ
通讯作者：
Kaufman RJ
DOI：
10.1126/science.1189157
发表时间：
2010-11-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Giorgi C;Ito K;Lin HK;Santangelo C;Wieckowski MR;Lebiedzinska M;Bononi A;Bonora M;Duszynski J;Bernardi R;Rizzuto R;Tacchetti C;Pinton P;Pandolfi PP
通讯作者：
Pandolfi PP
NADPH 氧化酶抑制剂罗布麻素可预防四氧嘧啶诱导的糖尿病兔的心房重构
影响因子：
3.5
作者：
Qiu, Jiuchun;Zhao, Jianping;Li, Guangping
通讯作者：
Li, Guangping
内膜的四十千克蛋白是线粒体钙Uniporter。
影响因子：
64.8
作者：
De Stefani, Diego;Raffaello, Anna;Teardo, Enrico;Szabo, Ildiko;Rizzuto, Rosario
通讯作者：
Rizzuto, Rosario
影响因子：
64.8
作者：
Baughman, Joshua M.;Perocchi, Fabiana;Girgis, Hany S.;Plovanich, Molly;Belcher-Timme, Casey A.;Sancak, Yasemin;Bao, X. Robert;Strittmatter, Laura;Goldberger, Olga;Bogorad, Roman L.;Koteliansky, Victor;Mootha, Vamsi K.
通讯作者：
Mootha, Vamsi K.