Downregulation of CREB-binding protein expression sensitizes endothelial cells to serum-deprived apoptosis: important role of nitric oxide.
Endothelium-derived nitric oxide (NO) is a cytoprotective molecule to prevent endothelial cells (ECs) from apoptosis. CREB-binding protein (CBP) is involved in the apoptotic pathway in several tumor cells, however, little is known whether CBP is associated with apoptosis in ECs and the apoptotic effect of CBP on ECs is regulated by NO. Therefore, the purpose of the present study was to investigate whether silencing CBP expression could affect the sensitivity of ECs toward apoptotic stimuli and determined the role of NO. In this study, we found that when CBP expression was silenced by RNA interference, ECs were more prone to apoptosis under serum deprivation, whereas the apoptosis was not significantly induced in the serum-containing condition. The increased apoptosis is paralleled by a reduction of NO, and the apoptosis was reversed by NO donors, suggesting an important role of NO. Furthermore, CBP silencing decreased NO production by downregulating the endothelial NO synthase (eNOS) expression in a dose-dependent manner. These results indicated that CBP silencing is associated with decreased eNOS expression and NO production, and therefore concomitantly increased the sensitivity of ECs toward apoptosis.
Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China.
Jing
J
Chen
Hong
H
Jiang
Li-hua
LH
Zhu
Lang
L
Wang
Lin
L
Xu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D050882:CREB-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics*; D016895:Culture Media, Serum-Free / Q000009:adverse effects / Q000494:pharmacology*; D015536:Down-Regulation / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D020030:Nitric Oxide Donors; D034741:RNA, Small Interfering; D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D050882:CREB-Binding Protein