The suppressive effect of a cytosolic Ca^<2+> chelator in superoxide-induced hepatocyte injury

胞浆Ca^2螯合剂对超氧化物诱导的肝细胞损伤的抑制作用

• 批准号: 07670594
• 负责人: UKIDA Minoru
• 金额: $ 1.34万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670594/
• 关键词: Oxidative stress; Lipid peroxidation; Calcium-ion homeostasis; Hepatocellular injury; Liver perfusion; Cyclosporin A; Superoxide; Mitochondorial membrane potential; 肝細胞傷害; カルシウムホメオスターシス; 肝灌流

In the study using primary cultured hepatocyrte, the cytosolic calcium ion chelator, 1,2-bis (O-aminophenoxy) ethane -N,N,N', N'-tetraacetic acid- acetoxymethylester (BAPTAAM) suppressed the hepatocellular injury by tert-butyl hydroperoxide (TBHP) at each extracellular calcium ion concentration of 0,1 and 3mM,indepent of the lipid peroxidation of the cell membrane and the mitochondrial membrane potential measured by Rhodamine 123. Therefore, the disturbance of cytosolic calcium homeostasis plays the major role in the hepatocellular injury by TBHP.In the study using isolated liver perfusion, the the hepatocellular injury by TBHP was minimum in the physiological perfusate Ca^<2+> concentration of 1.25mM compared with those of 0mM and 2.50mM.Under the each perfusate Ca^<2+> concentrations, Cyclospolin A (CsA) suppressed significantly the hepatocyte cell death. About the mechanism of the suppressive effect of CsA,a conclusion could not be drawn yet, since the present experimental sample was very small.

本研究采用原代培养的肝细胞，（O-氨基苯氧基）乙烷-N，N，N ′，N ′-四乙酸-乙酰氧基甲酯（BAPTAAM）在细胞外钙离子浓度分别为0、1和3 mM时抑制叔丁基过氧化氢（TBHP）引起的肝细胞损伤，与细胞膜脂质过氧化和罗丹明123测定的线粒体膜电位无关。在离体肝灌流实验中，TBHP对肝细胞的损伤在生理性灌流液Ca^<2+>浓度为1.25 mM时最小，而在生理性灌流液Ca ^<2 +>浓度为0 mM和2.50 mM时损伤最小。环孢素A（CsA）可明显抑制肝细胞死亡。关于CsA抑制作用的机制，由于目前的实验样本量很小，尚不能得出结论。

项目成果

Mikami M,Ukida M,et al: "The suppressive effect of a cytosolic calcium ion chelator on the hepatocellular injury by oxidative stress" International Hepatology Communication. (in press).

Mikami M，Ukida M，等人：“细胞质钙离子螯合剂对氧化应激引起的肝细胞损伤的抑制作用”国际肝病学通讯。

Masayuki Mikami: "The suppressive effect of a cytosolic calcium-ion chelator on the hepatocellular injury by oxidative stress." International Hepatology Communications. (in press).

Masayuki Mikami：“胞质钙离子螯合剂对氧化应激引起的肝细胞损伤的抑制作用。”

Yoshiyuki Nishikawa, kennji Jinnno, Minoru Ukida, Takao Tsuji: "A new measurement method of a viability of cultured cells using PI and Hoechst 33258 (in Japanese)" Molecular Medicine. 32 (12). 1340-1342 (1995)

Yoshiyuki Nishikawa、kennji Jinnno、Minoru Ukida、Takao Tsuji：“使用 PI 和 Hoechst 33258（日语）测量培养细胞活力的新方法”分子医学。