Opiates promote T cell apoptosis through JNK and caspase pathway.
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 NH2-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.
Singhal
P
P
Division of Kidney Diseases and Hypertension, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA.
Kapasi
A
A
Reddy
K
K
Franki
N
N
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000633:toxicity; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009020:Morphine / Q000633:toxicity; D009294:Narcotics / Q000633:toxicity*; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology
D009294:Narcotics; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases