Stimulation of p38 MAP kinase reduces acidosis and Na+ overload in preconditioned hepatocytes

FEBS Letters

Carini, Rita¹  Grazia De Cesaris, Maria¹  Splendore, Roberta¹  Albano, Emanuele¹ 

[1] Department of Medical Sciences, University ‘A. Avogagro’ of East Piedmont, Via Solaroli 17, 28100 Novara, Italy

关键词: Vacuolar proton ATPase;    Liver preconditioning;    Bafilomycin;    Acidosis;    Hypoxia;    Liver injury;    Liver transplantation;   

DOI  :  10.1016/S0014-5793(01)02189-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Ischemic preconditioning has been shown to improve liver resistance to hypoxia/reperfusion damage. A signal pathway involving A_2A-adenosine receptor, G_i-proteins, protein kinase C and p38 MAP kinase is responsible for the development of hypoxic preconditioning in hepatocytes. However, the coupling of this signal pathway with the mechanisms responsible for cytoprotection is still unknown. We have observed that stimulation of A_2A-adenosine receptors or of p38 MAPK by CGS21680 or anisomycin, respectively, appreciably reduced intracellular acidosis and Na⁺ accumulation developing during hypoxia. These effects were reverted by p38 MAPK inhibitor SB203580 as well as by blocking vacuolar proton ATPase with bafilomycin A₁. SB203580 and bafilomycin A₁ also abolished the cytoprotective action exerted by both CGS21680 and anisomycin. We propose that the stimulation of p38 MAPK by preconditioning might increase hepatocyte resistance to hypoxia by activating proton extrusion through vacuolar proton ATPase, thus limiting Na⁺ overload promoted by Na⁺-dependent acid buffering systems.

【 授权许可】

Unknown