Zhu Hong, Zhang Li, Xi Xiaoqing, Zweier Jay L, Li Yunbo
Department of Internal Medicine and Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine and Public Health, 473 West 12th Avenue, Columbus, OH 43210, USA.
Free Radic Res. 2006 Aug;40(8):875-84. doi: 10.1080/10715760600778694.
This study was undertaken to determine if 4-hydroxy-2-nonenal (HNE) could upregulate antioxidants and phase 2 enzymes in rat H9c2 myocardiac cells, and if the upregulated defenses led to cytoprotection against oxidative and electrophilic injury. Incubation of H9c2 cells with HNE at noncytotoxic concentrations resulted in significant induction of cellular catalase, glutathione (GSH), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase 1 (NQO1), as determined by enzyme activity and/or protein expression. HNE treatment caused increased mRNA expression of catalase, gamma-glutamylcysteine ligase, GST-A1, and NQO1. Pretreatment of H9c2 cells with HNE led to significant protection against cytotoxicity induced by reactive oxygen and nitrogen species. HNE-pretreated cells also exhibited increased resistance to injury elicited by subsequent cytotoxic concentrations of HNE. Taken together, this study demonstrates that several antioxidants and phase 2 enzymes in H9c2 cells are upregulated by HNE and that the increased defenses afford protection against overt oxidative and electrophilic cardiac cell injury.
本研究旨在确定4-羟基-2-壬烯醛（HNE）是否能上调大鼠H9c2心肌细胞中的抗氧化剂和Ⅱ相酶，以及上调的防御机制是否能对氧化和亲电损伤产生细胞保护作用。用非细胞毒性浓度的HNE孵育H9c2细胞，通过酶活性和/或蛋白质表达测定，结果显示细胞过氧化氢酶、谷胱甘肽（GSH）、谷胱甘肽S-转移酶（GST）和NAD(P)H:醌氧化还原酶1（NQO1）均有显著诱导。HNE处理导致过氧化氢酶、γ-谷氨酰半胱氨酸连接酶、GST-A1和NQO1的mRNA表达增加。用HNE预处理H9c2细胞可显著保护细胞免受活性氧和氮物种诱导的细胞毒性。经HNE预处理的细胞对随后细胞毒性浓度的HNE引起的损伤也表现出更高的抗性。综上所述，本研究表明HNE可上调H9c2细胞中的多种抗氧化剂和Ⅱ相酶，且增强的防御机制可保护心肌细胞免受明显的氧化和亲电损伤。
