Chloride Intracellular Channel 1 Promotes Endothelial Injury by Disturbing Mitochondrial Dynamic Balance

Abstract: This work studied the effect of chloride intracellular channel 1 (CLIC1) on H2O2 induced mitochondrial dynamics in human umbilical vein endothelial cells， and investigated the function and mechanism of CLIC1 in endothelial injury. For preparation， the human umbilical vein endothelial cells were treated with the specific inhibitor indanyloxyacetic acid 94 (IAA94) (40 μmol/L)， H2O2 (0.9 mmol/L) and H2O2 (0.9 mmol/L) combined with IAA94 (40 μmol/L)， respectively. The content of reactive oxygen species and MDA were determined by fluorescence method. Membrane potential was determined by JC-1. The mRNA expression of CLIC1， Drp1 and Mfn1 were determined by qPCR. The protein level of CLIC1 and Drp1 were determined by Western blot. The results showed that H2O2 could increase the content of oxidative damage factor ROS， MDA and CLIC1 (P<0.05) compared with the control group. The level of ATP (P<0.05) and membrane potential (P<0.001) were significantly reduced in HUVEC treated by H2O2. Moreover， the mRNA and protein expression level of mitochondrial division protein (P<0.05) was elevated while fusion protein (P<0.05) was reduced significantly. However， after 2 h pretreatment of IAA94， the expression of mitochondrial division protein (P<0.05) was decreased while fusion protein (P<0.05) was increased， membrane potential (P<0.001) were significantly increased， the content of SOD and MDA (P<0.001) were reduced. In conclusion， CLIC1 plays an important role in mitochondrial injury of endothelial cells induced by H2O2 and its mechanism may be related to the interference of the mitochondrial dynamic balance.

CSTR: 32200.14.cjcb.2018.10.0004