Adrenoreceptor-coupled signal-transduction mechanisms mediating lymphocyte apoptosis induced by endogenous catecholamines.
Our previous work has shown that lymphocytes synthesize catecholamines (CAs) and the endogenous CAs accelerate apoptosis of concanavalin A (Con A)-activated lymphocyte. Here, we explored the involvement of adrenoreceptors (ARs) and signal molecules coupled to the ARs in the endogenous CA-mediated modulation of lymphocyte apoptosis. Pargyline, an inhibitor of CA degradation, up-regulated the expression of cleaved caspase-3 protein and increased the number of apoptotic cells. Antagonists of alpha(1)-ARs and beta(2)-ARs, not antagonists of alpha(2)-ARs or beta(1)-ARs, blocked these effects of pargyline. The facilitating effects of pargyline on lymphocyte apoptosis were mimicked by activators of adenylate cyclase and PKC, but reversed by inhibitors of PKA, PLC and PKC. Pargyline-stimulated CREB activation and Smac/DIABLO expression were prevented by the inhibitors of PKA, PLC and PKC. These results imply that endogenous CA-induced lymphocyte apoptosis is mediated by cAMP-PKA- and PLC-PKC-linked CREB-Smac/DIABLO pathways coupled with alpha(1)-ARs and beta(2)-ARs.
Jiang
Jian-Lan
JL
Department of Biological Science and Technology, School of Life Sciences, Mailbox 426, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
Peng
Yu-Ping
YP
Qiu
Yi-Hua
YH
Wang
Jian-Jun
JJ
D000320:Adrenergic Fibers / Q000276:immunology / Q000378:metabolism; D058646:Adrenergic alpha-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D050882:CREB-Binding Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D010738:Type C Phospholipases / Q000378:metabolism
D058646:Adrenergic alpha-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D002395:Catecholamines; C489013:DIABLO protein, rat; D024101:Mitochondrial Proteins; D011941:Receptors, Adrenergic; D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D050882:CREB-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases