The inhibitory effect of quercetin on asymmetric dimethylarginine-induced apoptosis is mediated by the endoplasmic reticulum stress pathway in glomerular endothelial cells.
The inhibitory effect of quercetin on asymmetric dimethylarginine-induced apoptosis is mediated by the endoplasmic reticulum stress pathway in glomerular endothelial cells.
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DOI：
10.3390/ijms15010484
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发表时间：
2014-01-02
影响因子：
5.6
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Guo W;Ding J;Zhang A;Dai W;Liu S;Diao Z;Wang L;Han X;Liu W
不对称二甲基精氨酸（ADMA）被认为是慢性肾脏疾病（CKD）患者的独立死亡率和心血管危险因素，并有助于肾纤维化的发展。槲皮素（QC）是一种天然的食物成分，可以防止肾脏损伤。在这里，我们探讨了adma诱导肾纤维化的可能机制和QC的保护作用。我们发现ADMA激活内质网（ER）应激传感器蛋白磷酸化蛋白激酶rna激活样ER激酶（PERK）和肌醇需要-1α (IRE1)，从而诱导肾小球内皮细胞（GEnCs）中C/EBP同源蛋白（CHOP）表达和磷酸化的C - jun n -末端激酶（JNK）磷酸化。随后，ADMA促进内质网应激诱导的凋亡，并导致GEnCs中转化生长因子β (TGF-β)的表达。JNK抑制剂SP600125和CHOP siRNA可抑制adma诱导的细胞凋亡和TGF-β的表达。QC可阻止adma诱导的PERK和IRE1凋亡内质网应激途径的激活。adma诱导的GEnCs细胞凋亡和TGF-β表达减少。CHOP过表达阻断qc介导的内质网应激细胞凋亡保护。总之，这些观察结果表明ADMA可能通过靶向PERK-CHOP和IRE1-JNK通路诱导GEnCs凋亡和TGF-β表达。此外，针对内质网应激的QC等药物可能对开发抗adma诱导的肾纤维化的新疗法有很大的希望。
Asymmetric dimethylarginine (ADMA) is considered an independent mortality and cardiovascular risk factor in chronic kidney disease (CKD) patients, and contributes to the development of renal fibrosis. Quercetin (QC), a natural component of foods, protects against renal injury. Here, we explored the possible mechanisms that are responsible for ADMA-induced renal fibrosis and the protective effect of QC. We found that ADMA treatment activated the endoplasmic reticulum (ER) stress sensor proteins phosphorylated protein kinase RNA-activated-like ER kinase (PERK) and inositol requiring-1α (IRE1), which correspondingly induced C/EBP homologous protein (CHOP) expression and phosphorylated c-Jun N-terminal kinase (JNK) phosphorylation in glomerular endothelial cells (GEnCs). Following this, ADMA promoted ER stress-induced apoptosis and resulted in transforming growth factor β (TGF-β) expression in GEnCs. SP600125, an inhibitor of JNK, and CHOP siRNA protected against ADMA-induced cell apoptosis and TGF-β expression. QC prevented ADMA-induced PERK and IRE1 apoptotic ER stress pathway activation. Also, ADMA-induced GEnCs apoptosis and TGF-β expression was reduced by QC. Overexpression of CHOP blocked QC-mediated protection from apoptosis in ER stressed cells. Overall, these observations indicate that ADMA may induce GEnCs apoptosis and TGF-β expression by targeting the PERK-CHOP and IRE1-JNK pathway. In addition, drugs such as QC targeting ER stress may hold great promise for the development of novel therapies against ADMA-induced renal fibrosis.
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DOI：
10.1016/s0735-1097(01)01318-3
发表时间：
2001-07-01
影响因子：
24
作者：
Lundman, P;Eriksson, MJ;Tornvall, P
通讯作者：
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影响因子：
13.6
作者：
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影响因子：
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作者：
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影响因子：
13.6
作者：
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Fliser, D
DOI：
10.1152/ajpcell.1999.277.3.c403
发表时间：
1999-09-01
影响因子：
5.5
作者：
Kobuchi, H;Roy, S;Packer, L
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Packer, L