Endoplasmic reticulum stress response in spontaneously hypertensive rats is affected by myocardial ischemia reperfusion injury.
Endoplasmic reticulum stress response in spontaneously hypertensive rats is affected by myocardial ischemia reperfusion injury.
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DOI：
10.3892/etm.2014.2094
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发表时间：
2015-02
影响因子：
2.7
通讯作者：
Yang XJ
中科院分区：
文献类型：
--
作者：
Guo XF;Yang XJ
内质网应激诱导的细胞凋亡是心肌缺血/再灌注（MI/R）后心肌坏死的主要原因之一。C/EBP同源蛋白（CHOP）途径是内质网应激诱导细胞凋亡的主要途径。葡萄糖调节蛋白78 （Glucose-regulated protein 78, GRP78）是参与CHOP通路的重要蛋白。本研究探讨了MI/R通过信号通路激活CHOP通路的假设，该通路涉及pkr样ER激酶（PERK）、真核起始因子2α -亚基（eIF2α）和激活转录因子2 （ATF2）。自发性超敏大鼠心脏组织免疫组化染色显示，心肌梗死/R损伤增加CHOP和GPR78蛋白表达水平。为了进一步分析内质网应激诱导MI/R损伤凋亡的机制，我们检测了假设的PERK-eIF2α-ATF2通路中涉及的5种标记蛋白，即PERK、磷酸化PERK （P-PERK）、eIF2α、磷酸化eIF2α (P-eIF2α)和ATF2的表达水平。如果这些蛋白的集体表达水平升高，则表明该信号通路诱导了细胞凋亡。此外，本研究还通过卡托普利（一种有效的高血压治疗药物）治疗自发性高血压大鼠（SHRs），探讨高血压是否影响MI/ r诱导的心肌凋亡的信号通路。用卡托普利治疗的大鼠血压降至正常水平，但与未治疗的大鼠相比，测试蛋白的表达水平或心肌梗死/心肌梗死损伤严重程度没有显著差异。这些结果表明，MI/R通过激活PERK-eIF2α-ATF2通路激活内质网应激时CHOP通路，高血压不影响该信号通路。
Cell apoptosis induced by endoplasmic reticulum (ER) stress appears to be one of the main causes of myocardial necrosis following myocardial ischemia/reperfusion (MI/R). The C/EBP homologous protein (CHOP) pathway is the main pathway through which apoptosis is induced during ER stress. Glucose-regulated protein 78 (GRP78) is an important protein involved in the CHOP pathway. The present study investigated the hypothesis that MI/R activates the CHOP pathway through signaling via a pathway involving PKR-like ER kinase (PERK), α-subunit of eukaryotic initiation factor 2 (eIF2α) and activating transcription factor 2 (ATF2). Immunohistochemical staining of the heart tissues from spontaneously hypersensitive rats indicated that MI/R injury increases CHOP and GPR78 protein expression levels. To further analyze the mechanism by which MI/R injury induces apoptosis by ER stress, the expression levels of five marker proteins involved in the hypothetical PERK-eIF2α-ATF2 pathway were detected, namely PERK, phosphorylated PERK (P-PERK), eIF2α, phosphorylated eIF2α (P-eIF2α) and ATF2. An increase in the collective expression levels of these proteins would indicate that apoptosis was induced by this signaling pathway. In addition, the study also explored whether hypertension affects the signaling pathway of MI/R-induced myocardial apoptosis by treating spontaneously hypertensive rats (SHRs) with captopril (an effective drug used to treat hypertension). Rats treated with captopril experienced a reduction in blood pressure to normal levels, but no marked differences in the expression levels of the tested proteins or in MI/R injury severity compared with those in untreated rats. These results suggest that MI/R activates the CHOP pathway during ER stress by activating the PERK-eIF2α-ATF2 pathway and that hypertension does not affect this signaling pathway.
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阿利吉仑直接抑制肾素可通过激活自发性高血压大鼠的一氧化氮合酶信号来预防心肌缺血/再灌注损伤
影响因子：
5.4
作者：
Zhang W;Han Y;Meng G;Bai W;Xie L;Lu H;Shao Y;Wei L;Pan S;Zhou S;Chen Q;Ferro A;Ji Y
通讯作者：
Ji Y
影响因子：
6.1
作者：
Campos, Gisela;Schmidt-Heck, Wolfgang;Godoy, Patricio
通讯作者：
Godoy, Patricio
影响因子：
5.3
作者：
Bruhat, A;Jousse, C;Fafournoux, P
通讯作者：
Fafournoux, P
DOI：
10.1007/978-1-4614-3209-8_83
发表时间：
2014-01-01
期刊：
RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY
影响因子：
--
作者：
Chiang, Wei-Chieh Jerry;Lin, Jonathan H.
通讯作者：
Lin, Jonathan H.
DOI：
10.1155/2012/482905
发表时间：
2012
期刊：
Leukemia research and treatment
影响因子：
--
作者：
Ozpolat B;Akar U;Tekedereli I;Alpay SN;Barria M;Gezgen B;Zhang N;Coombes K;Kornblau S;Lopez-Berestein G
通讯作者：
Lopez-Berestein G