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N-acetyl-L-cysteine inhibits activitation of p38 MAP kinase in heat stressed heart

N-乙酰-L-半胱氨酸抑制热应激心脏中 p38 MAP 激酶的激活

基本信息

批准号：
11671507
负责人：
MOROOKA Hiroaki
金额：
$ 2.37万
依托单位：
NAGASAKI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671507/
关键词：
SAPK LNK p38 MAPK Ischemia-Reperfusion p38MAPK p38 MAP キナーゼ高体温

项目摘要

p38 mitogen-activated protein kinase (MAPK) plays an important role in regulating gene expression. p38 MAPK as well as stress-activated protein kinase (SAPK/JNK) is activated in response to a variety of cellular stresses, such as heat stress and oxidative stress. N-acetyl-L-cysteine ' (NAC), an antioxidant, increases the intracellular glutathione (GSH) levels and attenuates SAPK/JNK activity resulting in reduced cellular damage. We investigated the effect of NAC on the activatiomofp38 MAPK in heat stressed rat heart. 12 male Wistar rats were anesthetized with pentobarbital intraperitoneally (i.p.). Saline (n=6) or 1 mmol/kg NAC (n=6) were administered i.p. 60 min before treatment withbody temperature. Desired bodytemperature (37 or 41 C) was achieved by placing animals in a positive forced air incubator. Heart was removed 60 min follwing the samebodytemperature. p38 MAPK activity at 41 Cwas increased to 630±53 % of that at 37 C. NAC administration inhibited the activation of p38 MAPK activity at 41 C to 127± 21 % of that at 37 C. Our results indicate acomplex interactionbetweenheat stress and oxidative stress on activation of p38 MAPK in heart. Suppression of p38 MAPK activity by pretreatment with antioxidant may be one strategy for organ protection against thermal injury in heart.

p38丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）在基因表达调控中起重要作用。p38 MAPK以及应激活化蛋白激酶（SAPK/JNK）响应于多种细胞应激（例如热应激和氧化应激）而被激活。N-乙酰基-L-半胱氨酸（NAC）是一种抗氧化剂，其增加细胞内谷胱甘肽（GSH）水平并减弱SAPK/JNK活性，导致细胞损伤减少。本研究观察了NAC对热应激大鼠心脏p38 MAPK活化的影响。12只雄性Wistar大鼠用戊巴比妥腹腔内（i. p.）麻醉。6只大鼠在给药前60 min腹腔注射生理盐水或NAC 1 mmol/kg。通过将动物置于正压空气培养箱中达到所需体温（37或41 ℃）。在相同的体温下60分钟取出心脏。41 ℃时p38 MAPK活性增加至37 ℃时的630± 53%。在41 ℃时，NAC给药抑制了p38 MAPK活性，为37 ℃时的127± 21%。我们的研究结果表明热应激和氧化应激对心脏p38 MAPK激活之间存在复杂的相互作用。抗氧化剂预处理抑制p38 MAPK活性可能是心脏热损伤时器官保护的一种策略。