Apolipoprotein-J blocks increased cell injury elicited by ox-LDL via inhibiting ROS-CaMKII pathway

Lipids in Health and Disease

Shuying Qi¹  Yu Chen¹  Dongmei Wang¹  Leisheng Ru¹  Chao Ding¹  Zhi Gong¹  Yanzhuo Ma¹  Kai Nan² 

[1]0000 0000 8727 6165, grid.452440.3, Department of Cardiology, Bethune International Peace Hospital, 398, Zhongshan Road, 050082, Shijiazhuang, Hebei, China

[2]Health and Medical Development Research Center of Hebei Province, Shijiazhuang, Hebei, China

关键词: Ox-LDL;    Apolipoprotein-J;    Apoptosis;    Neonatal rat ventricular cells;   

DOI  :  10.1186/s12944-019-1066-8

来源: publisher

【 摘 要 】

BackgroundOxidized low-density lipoprotein (ox-LDL) is crucial in cardiac injury. Apolipoprotein-J (ApoJ) contributes to antiapoptotic effects in the heart. We aimed to evaluate the protective effects of ApoJ against ox-LDL cytotoxicity in Neonatal rat ventricular cells (NRVCs).Methods and resultsNRVCs were damaged by exposure to ox-LDL, as shown by increased caspase-3/7 activity, enhanced caspase-3 expression, and decreased cell viability. ApoJ overexpression, using an adenovirus vector, significantly reduced ox-LDL-induced cell injury. ApoJ also prevented ox-LDL from augmenting reactive oxygen species (ROS) production, as demonstrated by elevated Nox2/gp91phox and P47 expression. Furthermore, ApoJ overexpression reduced CaMKIIδ expression elicited by ox-LDL in cultured NRVCs. Upregulating CaMKIIδ activity, mediated by ox-LDL, was significantly inhibited by ApoJ overexpression. A CaMKIIδ inhibitor, KN93, prevented ApoJ’s protective effect against ox-LDL cytotoxicity. A ROS scavenger, Mn (III)meso-tetrakis (4-benzoic acid) porphyrin (Mn (III)TBAP), also attenuated CaMKIIδ’s increased expression and activity, induced by ox-LDL, and showed similar results to ApoJ by attenuating ox-LDL-induced cell damage, as ApoJ did.ConclusionsApoJ confers cytoprotection to NRVCs against ox-LDL cytotoxicity through the ROS-CaMKII pathways.

【 授权许可】

CC BY