Role of nitric oxide increase on induced programmed cell death during early stages of rat liver regeneration
Role of nitric oxide increase on induced programmed cell death during early stages of rat liver regeneration
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DOI：
10.1016/j.bbadis.2004.05.004
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发表时间：
2004-09-06
影响因子：
6.2
通讯作者：
Carnovale, CE
中科院分区：
文献类型：
--
作者：
Ronco, MT;Alvarez, MD;Carnovale, CE
分析了NO在肝再生过程中调节细胞增殖与凋亡平衡的可能细胞机制。在再生过程的早期阶段，我们通过脂多糖（LPS）诱导诱导型一氧化氮合酶（iNOS）和直接NO供体（硝普钠（SNP））增加NO来测定p53、促凋亡蛋白Bax、抗凋亡Bcl-x（L）、增殖细胞核抗原（PCNA）和凋亡指数。将雄性Wistar大鼠随机分为四个实验组：假手术对照组（Sh）、部分肝切除对照组（PH-C）、用LPS（2 mg/kg体重，i. p.）（PH-LPS），并用SNP（2.5 mg/kg体重，以1 ml/h的速率静脉内注射）预处理的部分肝切除（PH-SNP）。术后5 h处死动物。PH-C组大鼠肝细胞质iNOS水平较Sh组增加34%，LPS组iNOS蛋白水平较PH-C组增加30%。Bax和p53蛋白水平在LPS和SNP处理的肝切除大鼠中相对于PH-C显著增加。PH-LPS和PH-SNP组细胞凋亡指数均较PH-C组增加75%。NO的增加并未表现出增殖过程的任何变化。这些结果表明，NO参与细胞凋亡通过p53和Bax蛋白后PH，显示出严格调节的生长过程中的肝再生。(C)2004 Elsevier B. V.保留所有权利。
We analysed the possible cellular mechanism involved in the NO action in the balance between apoptosis and cell proliferation in liver regeneration process. We determined p53, proapoptotic protein Bax, antiapoptotic Bcl-x(L), proliferating cell nuclear antigen (PCNA) and apoptotic index at the early stages of regenerative process after NO increase by lipopolysaccharide-induction (LPS) of inducible-type nitric oxide synthase (iNOS) and by direct NO donor (sodium nitroprusside, SNP). Male Wistar rats were randomised in four experimental groups: sham operated control (Sh), partial hepatectomised control (PH-C), partial hepatectomised pretreated with LPS (2 mg/kg body weight, i.p.) (PH-LPS), and partial hepatectomised pretreated with SNP (2.5 mg/kg body weight, i.v. at a rate of 1 ml/h) (PH-SNP). Animals were killed 5 h post-surgery. Hepatic cytosolic iNOS showed an increase of 34% in PH-C animals with respect to Sh, and LPS-treatment increased iNOS protein levels 30% compared with PH-C. Bax and p53 protein levels showed significant increases in LPS- and SNP-treated hepatectomised rats with respect to PH-C. The apoptotic indexes were increased 75% in both, PH-LPS and PH-SNP rats versus PH-C. The increase of NO did not show any change in the proliferation process. These results suggest that NO is involved in apoptosis via p53 and Bax proteins after PH, showing a tightly regulated growth process in liver regeneration. (C) 2004 Elsevier B.V. All rights reserved.