Candesartan attenuates Angiotensin II-induced mesangial cell apoptosis via TLR4/MyD88 pathway.
Angiotensin II (Ang II) can stimulate Toll-like receptor 4 (TLR4) expression in mesangial cells (MCs), but the role of TLR4 in the Ang II-induced apoptosis and the effect of candesartan on TLR4 expression remain unclear. Here, we report that Ang II-induced MC apoptosis in a time-dependent manner and up-regulated TLR4/MyD88 expression, and that the intracellular ROS was subsequently increased. We also show that candesartan attenuated the Ang II-induced MC apoptosis, and that this protective effect was dependent on decreased TLR4/MyD88 expression as well as reduced intracellular ROS formation. Furthermore, Ang II increased the apoptosis inducing factor protein level, while candesartan markedly reduced this increase. These results demonstrate that TLR4/MyD88 pathway was involved in the Ang II promoted MC apoptosis, which was related to TLR4/MyD88 mediated oxidative stress. These data also suggest that candesartan exerted anti-apoptotic effect as an antioxidant by modulating this pathway.
Lv
Jinlei
J
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
Jia
Ruhan
R
Yang
Dingping
D
Zhu
JiLi
J
Ding
Guohua
G
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D002460:Cell Line; D050527:Mesangial Cells / Q000187:drug effects*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000378:metabolism*
D000975:Antioxidants; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D053594:Myeloid Differentiation Factor 88; D017382:Reactive Oxygen Species; D013777:Tetrazoles; D051197:Toll-Like Receptor 4; D000804:Angiotensin II; C081643:candesartan