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Morphine suppresses lymphocyte apoptosis by blocking p53-mediated death signaling
Shunji Suzuki1, Linda F Chuang, Roy H Doi
1Department of Medical Pharmacology and Toxicology, School of Medicine, University of California, Davis, CA 95616, USA.
Abstract:
Opiates such as morphine or heroin may promote cell apoptosis and cause dysfunction of immune cells. In simian immunodeficiency virus (SIV)-infected lymphocytic cells, however, morphine may protect the cells from apoptotic lysis and allow the virus to continue to replicate. To further explore this apparently antithetical effect of opiates, we evaluated in the present study the effects of morphine on human lymphocytic CEM x174 cells induced to undergo apoptosis in the presence of actinomycin D. It was found that induction of apoptosis (characterized by DNA laddering) by actinomycin D was accompanied by a stimulation of the expression of active (phosphorylated) form of p53. Pretreatment of the cells with 10nM morphine caused a transient, naloxone-reversible suppression of the appearance of activated p53 and the generation of DNA laddering. Parallel evaluation of the growth of CEM x174 indicated that morphine treatment delays the inception of cell death triggered by actinomycin D. Inasmuch as Bcl-2 suppresses while Bax accelerates apoptosis, treatment of cells with morphine reduced the expression of Bax and enhanced the expression of Bcl-2. Taken together, morphine, through binding at the opioid receptor, may protect lymphocytic cells from apoptotic lysis if cell death is initiated by apoptosis-inducing agents such as human immunodeficiency virus (HIV), SIV or actinomycin D.
Insights
Morphine protects human lymphocytic cells from apoptosis induced by agents like actinomycin D. This effect, mediated by opioid receptors, involves regulating p53, Bax, and Bcl-2 expression, potentially impacting viral replication.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Opiates like morphine can induce apoptosis and immune cell dysfunction.
- However, morphine may protect simian immunodeficiency virus (SIV)-infected cells from apoptosis, allowing viral replication.
Purpose of the Study:
- To investigate the effects of morphine on apoptosis in human lymphocytic CEM x174 cells.
- To explore the molecular mechanisms underlying morphine's potential protective role against apoptosis.
Main Methods:
- Induction of apoptosis in CEM x174 cells using actinomycin D.
- Treatment with morphine and naloxone to assess opioid receptor involvement.
- Analysis of p53 activation, DNA laddering, and expression of apoptosis-related proteins (Bcl-2, Bax).
Main Results:
- Actinomycin D induced apoptosis, characterized by p53 activation and DNA laddering.
- Morphine pretreatment transiently suppressed p53 activation and DNA laddering in a naloxone-reversible manner.
- Morphine treatment reduced Bax expression and increased Bcl-2 expression, delaying cell death.
Conclusions:
- Morphine, via opioid receptor binding, may protect lymphocytic cells from apoptosis induced by agents like HIV, SIV, or actinomycin D.
- This protective effect is associated with modulation of p53, Bax, and Bcl-2 pathways.