Abstract：To investigate the effect of heat stress on the antioxidant function in relation to the mRNA expression of Keap1 (kelch-like ECH-associated protein-1)/Nrf2（NF-E2-related factor 2）/ARE (antioxidant response element) in mouse liver, male mice of 8weeks were placed in 42 ℃ for 2 hours of 12 successive days. The mice were sacrificed on days 0 (control), 1, 2, 4, 8 and 12 immediately following heat stress. The body surface temperature and rectal temperature were found markedly increased, together with severe damage of the liver with the hyperemia and cellular edema. Hepatic MDA increased significantly at day 2 comparing with the level of control. Hepatic GSH level, GSH-PX and T-SOD activities increased at day 4 and 12. Immunohisto chemistry showed Nrf2 protein expression on day 1 through day 8, with a peak at day 4. Comparing to the control, the Keap1 mRNA expression decreased significantly at day 1, whereas the Nrf2 mRNA level increased at days 4 and 12. The HO-1 mRNA expression increased at day 1; NQO1 and GCLC increased at days 1 and 4. The results suggest that heat could induce oxidative stress in the liver with the involvement Keap1/Nrf2/ARE signal pathway.
王菲, 黄毅, 李延森, 曹云, 普少瑕, 李春梅. Keap1/Nrf2/ARE通路相关基因在热诱导的氧化应激小鼠肝脏中的表达[J]. 中国生物化学与分子生物学报, 2014, 30(3): 284-290.
WANG Fei, HUANG Yi, LI Yan-Sen, CAO Yun, PU Shao-Xia, LI Chun-Mei. Expression of Keap1/Nrf2/ARE Pathway-related Genes in Protective Response to Heat-induced Oxidative Stress in the Liver of Mice. Chinese Journal of Biochemistry and Molecular Biol, 2014, 30(3): 284-290.
毛帅,董虹,许剑琴,等. 抗应激中药冲剂对猪肝脏热应激蛋白 70 表达的影响[J]. 北京农学院学报(Mao S, Dong H, Xu J Q, et al. Effect of anti-stress pulvis from chinese herb on expression of heat stress protein 70 in pig liver[J]. J Beijing Univ Agric), 2008, 23(1): 50-53
Freeman B A, Crapo J D. Biology of disease: free radicals and tissue injury [J]. Lab Invest, 1982, 47(5): 412-426
蔡维霞,张军,胡大海. 氧化和化学应激的防御性转导通路—Nrf2/ARE[J].中国生物化学与分子生物学报(Cai W X, Zhang J, Hu D H. Defensive pathway of Nrf2/ARE involved in oxidative and chemical stress[J]. Chin J Biochem Mol Biol), 2009, 25(4): 297-303
Zhang D D. Mechanistic studies of the Nrf2-Keap1 signaling pathway[J]. Drug Metab Rev, 2006, 38(4): 769-789
李煌元,石年. Keap1-Nrf2/ARE通路在分子毒理学中的研究进展[J]. 国外医学:卫生学分册(Li HY, Shi N. The research progress of Keap1-Nrf2/ARE pathway in molecular toxicology[J]. Foreign Med Sci(Hyg)), 2006, 33(3) : 129-135
刘芳,杜志银,王应雄. Keap1在氧化应激方面的研究进展[J]. 中国临床药理学与治疗学(Liu F, Du Z Y, Wang Y X. Progress in study on relationship of Keap1 with oxidative stress[J].Chin J Clin Pharmacol Ther), 2010, 15(5) : 596-600
Yu J, Liu F, Yin P, et al. Integrating miRNA and mRNA expression profiles in response to heat stress-induced injury in rat small intestine[J]. Funct Integr Genomics, 2011, 11(2): 203-213
Harikai N, Sugawara T, Tomogane K, et al. Acute heat stress induces jumping escape behavior in mice[J]. Physiol Behav, 2004, 83(3): 373-376
Roberts W W, Mooney R D, Martin J R. Thermoregulatory behaviors of laboratory rodents[J]. J Comp Physiol Psychol, 1974, 86(4): 693-699
宁章勇,刘思当,赵德明,等. 热应激对肉仔鸡呼吸、消化和内分泌器官的形态和超微结构的影响[J]. 畜牧兽医学报(Ning Z Y, Liu S D, Zhao D M, et al. The influence of heat stress on morphological and ultrastructure change of respiratory, digestive and endocrine tissues in broilers[J].Acta Vet Zootech Sin), 2003, 34(6): 558-561
Ikeda M, Kodama H, Fukuda J, et al. Role of radical oxygen species in rat testicular germ cell apoptosis induced by heat stress[J]. Biol Reprod, 1999, 61(2): 393-399
Ji L L. Antioxidants and oxidative stress in exercise[J]. Exp Biol Med, 1999, 222(3): 283-292
Niess A M, Dickhuth H H, Northoff H, et al. Free radicals and oxidative stress in exercise- immunological aspects[J]. Exerc Immunol Rev, 1999, 5: 22-56
Wells P G, Kim P M, Laposa R R, et al. Oxidative damage in chemical teratogenesis[J]. Mutat Res, 1997, 396(1-2): 65-78
Droge W. Free radicals in the physiological control of cell function[J]. Physiol Rev, 2002, 82(1): 47-95
Gutteridge JM, Halliwell B. Comments on review of Free Radicals in Biology and Medicine, second edition, by Barry Halliwell and John M.C.Gutteridge[J].Free Radic Biol Med, 1992, 12(1): 93-95
Kim K J, Hong H D, Lee O H, et al. The effects of Acanthopanax senticosus on global hepatic gene expression in rats subjected to heat environmental stress[J]. Toxicology, 2010, 278(2): 217-223
Zhang H J, Drake V J, Morrison J P, et al. Selected contribution: differential expression of stress-related genes with aging and hyperthermia [J]. J Appl Physiol, 2002, 92(4): 1762-1769
Zhang H J, Xu L J, Drake V J, et al. Heat-induced liver injury in old rats is associated with exaggerated oxidative stress and altered transcription factor activation [J]. FASEB J, 2003, 17(15): 2293-2295
Ando M, Katagiri K, Yamamoto S, et al. Age-related effects of heat stress on protective enzymes for peroxides and microsomal monooxygenase in rat liver[J]. Environ Health Perspect, 1997, 105(7): 726-733
Bhusari S, Hearne L B, Spiers D E, et al. Transcriptional pro?ling of mouse liver in response to chronic heat stress[J]. J Therm Biol, 2008, 33(3): 157-167
Shih P H, Yen G C. Differential expression of antioxidant status in aging rats: the role of transcriptional factor Nrf2 and MAPK signaling pathway[J]. Biogerontology, 2007, 8(2): 71-80
Zou X, Feng Z, Li Y , et al. Stimulation of GSH synthesis to prevent oxidative stress-induced apoptosis by hydroxytyrosol in human retinal pigment epithelial cells: activation of Nrf2 and JNK-P62/SQSTM1 pathway[J]. J Nutr Biochem, 2012, 23(8): 994-1006
