Morphine-promoted survival of CEM x 174 cells in early stages of SIV infection in vitro: involvement of the multiple molecular mechanisms

Progression of HIV infections to AIDS is a complex process and it differs considerably among individuals infected with HIV, influenced by both genetic and environmental factors. Opiates have been implicated to be a cofactor in HIV infections leading to AIDS. However, little is known about the molecular mechanisms involved in the effects of opioids on HIV infected immune cells. Cell cycle analysis was carried out by flow cytometry, the phosphorylation of mitogen-activated protein kinases ERK1 and ERK2 was detected by Western blotting assay, and changes of calcium concentration were monitored by scanning intracellular fluorescence intensity. In response to the treatment with morphine, SIV-infected cells were accumulated in G1 phase. Morphine increased the content of intracellular calcium in a time-dependent manner. In addition, morphine also elevated the levels of PKC activity and phosphorylated ERK1/2. Therefore, it is implicated that the calcium-PKC-MAPK cascade is involved in morphine-prolonged survival of SIV-infected cells in the early stages of virus infection. (C) 2004 Elsevier Ltd. All rights reserved.ToxicologySCI(E)PubMed10ARTICLE4449-4561