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Different roles of ERK1/2 and p38 MAPKα/β in cellular signaling during cardiomyocyte anoxia preconditioning
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- Author:
- No author available
- Journal Title:
- ACTA PHYSIOLOGICA SINICA
- Issue:
- 4
- DOI:
- 10.3321/j.issn:0371-0874.2003.04.015
- Key Word:
- 生理学;心肌保护;缺氧;心肌缺血预处理;丝裂素活化蛋白激酶p38;细胞外信号调节蛋白激酶;大鼠
Abstract： 建立培养乳鼠心肌细胞的缺氧/复氧(A/R)损伤模型和缺氧预处理(APC)模型, 以细胞存活率、细胞内超氧化物趋化酶(SOD)活性、丙二醛(MDA)含量、培养上清液乳酸脱氢酶(LDH)活性作为反映心肌细胞损伤的指标.采用细胞外信号调节蛋白激酶(ERK1/2)抑制剂PD98059及丝裂素活化蛋白激酶p38α/β (p38α/β)阻滞剂SB203580干预模型, 并以胶内原位磷酸化法测定ERK1/2和p38 活性, 借以探讨ERK1/2和p38α/β在缺氧预处理保护机制中的作用.结果表明: (1)在APC组, 于预处理的缺氧时相给予PD98059, 可以完全消除APC的延迟保护作用; 在A/R组的缺氧时相加入PD98059对细胞损伤无影响; (2)在APC组的预处理缺氧时相给予p38α/β抑制剂SB203580并不能消除APC的保护作用, 而在A/R组的持续缺氧时相给予SB203580则可显著减轻缺氧对细胞的损伤; (3) ERK1/2和p38总活性测定表明, 缺氧可激活ERK1/2和p38, 它们的活性在缺氧后4 h时达到高峰, 而经过APC处理后, 两者活性高峰提前于缺氧后3 h时出现, 且峰值显著降低.上述结果提示, 预处理过程中ERK1/2的激活可能是缺氧预处理延迟保护机制中细胞信号传递的重要环节, 预处理阶段p38α/β的活化不参与APC诱导的延迟保护信号传递过程, p38 的过度激活可能是缺氧/复氧损伤过程中的一个致损伤参与因素, 而预处理抑制随后持续缺氧阶段p38的过度激活可能是其保护机制的一个环节.
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