Diallyl disulfide and diallyl trisulfide protect endothelial nitric oxide synthase against damage by oxidized low-density lipoprotein.
Garlic is viewed as an effective health food against atherosclerosis. In this study, we examined whether diallyl disulfide (DADS) and diallyl trisulfide (DATS) protect endothelial nitric oxide synthase (eNOS) activation against oxidized LDL (ox-LDL) insult and through what mechanism. We found that DADS and DATS reversed the suppression of eNOS Ser1177 phosphorylation by ox-LDL, and wortmannin abolished the reversal by DADS and DATS. Similarly, the inhibition of cellular cGMP and nitric oxide production by ox-LDL was reversed by DADS and DATS (p<0.05). This increase in nitric oxide bioavailability by the allyl sulfides was attenuated by wortmannin. Immunoprecipitation assay revealed that DADS and DATS preserved the interaction of eNOS with caveolin-1 in the membrane. In addition, DADS and DATS suppressed the reduction of the cellular eNOS protein content by ox-LDL. When cycloheximide was added to block protein synthesis, DADS and DATS suppressed eNOS protein degradation similarly to that noted by MG132. Ox-LDL increased chymotrypsin-like proteasome activity, and this increase was inhibited by the allyl sulfides and MG132 (p<0.05). These results suggest that DADS and DATS protect eNOS activity against ox-LDL insult. This protection can be attributed partly to their mediation of phosphatidylinositol 3-kinase/protein kinase B signaling and prevention of eNOS degradation.
Lei
Yen-Ping
YP
Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan.
Liu
Cheng-Tzu
CT
Sheen
Lee-Yan
LY
Chen
Haw-Wen
HW
Lii
Chong-Kuei
CK
D000498:Allyl Compounds / Q000494:pharmacology*; D051242:Caveolin 1 / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D017931:DNA Primers; D004220:Disulfides / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005737:Garlic; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013440:Sulfides / Q000494:pharmacology*; D014471:Umbilical Veins / Q000502:physiology
D000498:Allyl Compounds; D051242:Caveolin 1; D017931:DNA Primers; D004220:Disulfides; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D013440:Sulfides; C099252:oxidized low density lipoprotein; C042577:diallyl trisulfide; C028009:diallyl disulfide; D052250:Nitric Oxide Synthase Type III; D046988:Proteasome Endopeptidase Complex; D006152:Cyclic GMP