Abstract
Opiate addicts are prone to recurrent infections. In the present study we evaluated the molecular mechanism of opiate-induced T cell apoptosis. Both morphine and DAGO ([D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin) enhanced T cell apoptosis. Morphine as well as DAGO activated c-Jun NH 2 -terminal kinase (JNK) in T cells. Moreover, opiates increased the expression of ATF-2, a specific substrate for JNK and P38 mitogen activated kinases (MAPK). Furthermore, opiates attenuated extracellular signal related kinase (ERK) in T cells. Both morphine and DAGO cleaved pro-caspases 8, 9, and 10 and generated caspases 8, 9 and 10 (active products). Morphine as well as DAGO also cleaved poly- (ADP-ribose) polymerase (PARP) into 116 and 85 kD proteins indicating the activation of caspase-3. These results suggest that opiate-induced T cell apoptosis may be mediated through the JNK cascade and activation of caspases 8 and 3.
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Singhal, P., Kapasi, A., Reddy, K., Franki, N. (2002). Opiates Promote T Cell Apoptosis Through JNK and Caspase Pathway. In: Friedman, H., Klein, T.W., Madden, J.J. (eds) Neuroimmune Circuits, Drugs of Abuse, and Infectious Diseases. Advances in Experimental Medicine and Biology, vol 493. Springer, Boston, MA. https://doi.org/10.1007/0-306-47611-8_15
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DOI: https://doi.org/10.1007/0-306-47611-8_15
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