Morphine aggravates the apoptosis of simian immunodeficiency virus infected CEM x174 cells in the prolonged culture in vitro.
This study was designed to assess the in vitro effects of morphine on the lymphocytes infected with SIV. CEM x174 cells were cotreated with morphine and simian immunodeficiency virus (SIVmac239). Cells were cultured for 96 h and the effects of morphine on the viability of infected cells were determined. At the concentration of 1 micromol/l, morphine could inhibit the proliferation of CEM x174 cells at the culture of 72 h. The stronger effect was observed in the case of viral infection. During 72 h SIV loading, the cells were accumulated in S phase in all SIV infected groups. The S arrest was observed in every experimental group and statistically different from normal groups (P<0.05). The results from annexin V binding assay showed that SIV infection resulted in a lower proportion of vital cells and higher mortality compared with corresponding control (P<0.01). Morphine failed to induce detectable alteration in the cell cycle profile of viral infected cells. Western blotting showed that the synthesis of intracellular p53 and bax protein was gradually up-regulated in the virus-loading period of 72 h. Naloxone had an apparent additive rather than antagonistic effect on the morphine-associated enhancement of bax expression. The ratio of bax/bcl-2 proteins appeared to tilt the balance toward apoptosis. At 72 h of infection, 1 micromol/l of morphine significantly elevated the level of caspase-3. These results indicated that the alteration in the balance of intracellular apoptotic and anti-apoptotic elements is one of the reasons of accelerated progression of acquired immunodeficiency syndrome (AIDS) by opioids abuse.
Xu
Jin
J
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100083, China.
Li
Ping-Feng
PF
Liu
Xin-Hua
XH
Li
Gang
G
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006822:Hybrid Cells; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000235:genetics; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology*; D013778:Tetrazolium Salts; D013844:Thiazoles
D017304:Annexin A5; D008233:Lymphotoxin-alpha; D009294:Narcotics; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D009020:Morphine; C022616:thiazolyl blue