INVOLVEMENT OF THE Ca^2＋-PROTEIN KINASE C AND ADENYLATE CYCLACE SIGNAL PATHWAYS IN THE ACTIVATION OF THYMOCYTES IN RESPONSE TO WHOLE-BODY IRRADIATION WITH LOW DOSE X-RAYS

Objective. To study the molecular mechanism of the stimulatory effect of low dose radiation(LDR) on T cell activation. Methods. Thymocytes from Kunming mice exposed to whole-body irradiation(WBI) with different doses of X-rays were analyzed for the changes in signal molecules of the phospholipase C-phos-phatidylinositol biphosphate(PLC-IP2) and G protein-adenylate cyclase(AC) pathways. Results. It was found thatCa^2 ]i increased in response to doses within 0. 2 Gy which was most marked after 0. 075 Gy and the increase was accentuated in the presence of Con A. The changes in CD3 and cal-cineurin (CN) expression of the thymocytes followed the same pattern as the alterations in Ca^2 ]i after LDR. The expression of α,β1 and β2 isoforms of protein kinase C(PKC) was all up-regulated after 0. 075 Gy with the increase in PKC-β1 expression being most marked. The cAMP/cGMP ratio and PKA activity of the thymocytes was lowered after low dose radiation and increased after doses above 0. 5 Gy in a dose-de-pendent manner, thus giving rise to J-shaped dose-response curves. The Ca antagonist TMB-8 and cAMP stimulant cholera toxin suppressed the augmented thymocyte proliferation induced by LDR. Conclusion. Data presented in the present paper suggest that activation of the PLC-PIP2 signal path-way and suppression of the AC-cAMP signal pathway are involved in the stimulation of the thymocytes fol-lowing WBI with low dose X-rays.

INVOLVEMENT OF THE Ca2+-PROTEIN KINASE C AND ADENYLATE CYCLACE SIGNAL PATHWAYS IN THE ACTIVATION OF THYMOCYTES IN RESPONSE TO WHOLE-BODY IRRADIATION WITH LOW DOSE X-RAYS

OBJECTIVE: To study the molecular mechanism of the stimulatory effect of low dose radiation (LDR) on T cell activation. METHODS: Thymocytes from Kunming mice exposed to whole-body irradiation (WBI) with different doses of X-rays were analyzed for the changes in signal molecules of the phospholipase C-phosphatidylinositol biphosphate (PLC-IP2) and G protein-adenylate cyclase (AC) pathways. RESULTS: It was found that Ca2+]i increased in response to doses within 0. 2 Gy which was most marked after 0. 075 Gy and the increase was accentuated in the presence of Con A. The changes in CD3 and calcineurin (CN) expression of the thymocytes followed the same pattern as the alterations in Ca2+]i after LDR. The expression of alpha, beta1 and beta2 isoforms of protein kinase C (PKC) was all up-regulated after 0.075 Gy with the increase in PKC-beta1 expression being most marked. The cAMP/cGMP ratio and PKA activity of the thymocytes was lowered after low dose radiation and increased after doses above 0. 5 Gy in a dose-dependent manner, thus giving rise to J-shaped dose-response curves. The Ca antagonist TMB-8 and cAMP stimulant cholera toxin suppressed the augmented thymocyte proliferation induced by LDR. CONCLUSION: Data presented in the present paper suggest that activation of the PLC-PIP2 signal pathway and suppression of the AC-cAMP signal pathway are involved in the stimulation of the thymocytes following WBI with low dose X-rays.