期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 9, 期 7, 页码 817-828出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2007.1509
关键词
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资金
- NHLBI NIH HHS [R01 HL070726, HL70726, HL57244, R01 HL075316] Funding Source: Medline
- NIDDK NIH HHS [R01 DK054927, DK54927] Funding Source: Medline
This study examined the role of acid sphingomyelinase (ASM) and its redox amplification in mediating the formation of lipid raft (LR) redox signaling platforms in coronary arterial endothelial cells (CAECs). Using small interference RNA ( siRNA) of ASM, Fas ligand (FasL)-induced increase in ASM activity, production of ceramide, and LR clustering in CAECs were blocked, and clustered Fas was also substantially reduced in detergent-resistant membrane fractions of CAECs. LR clustering, gp91(phox) aggregation, and p47(phox) translocation to the LR clusters induced by FasL were also blocked in ASM-siRNA transfected CAECs. Corresponding to this reduction of LR clustering with NAD(P)H oxidase subunits in ASM-siRNA transfected CAECs, superoxide (O-2(-center dot)) production was significantly decreased as measured by either ESR or fluorescent spectrometry. Interestingly, superoxide dismutase ( SOD) not only scavenged O-2(-center dot), but also markedly attenuated LR clustering. Xanthine/xanthine oxidase, an exogenous O-2(-center dot) generating system, dramatically increased ASM activity and LR clustering in EC membrane and enhanced FasL-induced LR clustering, which were blocked by SOD. These results suggest that that ASM activates LR clustering to form redox signaling platforms, where O-2(-center dot) production enhances ASM activity, and thereby results in a forwarding amplification of LR and redox signaling. This ASM-mediated feedforwarding mechanism may be critical for an efficient transmembrane signaling through LRs.
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