title: Systematical analysis of impacts of heat stress on the proliferation, apoptosis and metabolism of mouse hepatocyte.
abstract: Heat stress will stimulate cells of living organisms to generate heat shock proteins (Hsps). In the mouse liver, impacts of heat stress on hepatocyte proliferation, apoptosis and metabolism have not been studied systematically at different temperatures. In this research, the test mice were heated to 40, 42, 44 and 46°C, respectively, for 20 min and recovered at room temperature for 8 h in normal feeding conditions; the control animals were kept at room temperature without heat stress. The expression levels of Hsp70, Pcna, Bax, Bcl2, cytochrome P450 1A2 (CYP1A2), CYP2E1 and analog of CYP3A4 (not reported in mouse before), the parameters reflecting stress strength, cell proliferation, apoptosis and metabolism, were detected by western blotting, immunohistochemistry and semi-quantitative RT-PCR in test and control mice. Haematoxylin-eosin (H&E) staining and TUNEL analysis were further used to study the impacts of heat stress at different temperatures on hepatocellular necrosis and apoptosis. Serum AST and ALT levels, the markers of liver injury, were measured after heat stress at different temperatures. The data show that Hsp70 expression was significantly increased when temperature increased (P < 0.05). At lower temperatures (40 or 42°C), expression of Pcna, CYP1A2 and analog of CYP3A4 were considerably increased (P < 0.05) while hepatocyte necrosis and apoptosis were not induced (P > 0.05). At higher temperatures (44 or 46°C), expression of Pcna was decreased while hepatocyte necrosis and apoptosis were induced (P < 0.05). Expressions of CYP1A2 and analog of CYP3A4 were decreased especially at 46°C (P < 0.05). Expression of CYP2E1 could not be detected to increase at 40°C but was at high levels at 42, 44 and 46°C (P < 0.05). Expressions of AST and ALT were not different between the test mice and control mice at 40°C while they were significantly higher in the test mice than those in the control mice at 42 (P < 0.05), 44 and 46°C (P < 0.01). In conclusion, heat stress at lower temperatures promotes hepatocyte proliferation and improves the metabolic efficiency in mouse liver while heat stress at higher temperatures inhibits hepatocyte proliferation, promotes hepatocyte apoptosis and induces hepatocyte necrosis. This may give a hint to understanding human liver injury in high temperatures. Moreover, it is the first time that the analog of CYP3A4 was detected in mouse hepatocellular cytoplasm. It is worthwhile to dissect its function in future work.
authors: The Key Laboratory of Pharmacology and Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Medical College, Henan University of Science and Technology, People's Republic of China. sanqiangli2001@163.com
authors: San-Qiang
authors: SQ
authors: Li
authors: Rui-Fang
authors: RF
authors: Li
authors: Shou-Min
authors: SM
authors: Xi
authors: Shu
authors: S
authors: Hu
authors: Zhi-Qiang
authors: ZQ
authors: Jia
authors: Shao-Ping
authors: SP
authors: Li
authors: Xin-Li
authors: XL
authors: Wen
authors: Ya-Kun
authors: YK
authors: Song
authors: Shuai
authors: S
authors: Li
authors: Shi-Peng
authors: SP
authors: Li
authors: Fei-Biao
authors: FB
authors: Wei
authors: Xue-Liang
authors: XL
authors: Chen
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D049109:Cell Proliferation; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D018882:Heat Stress Disorders / Q000503:physiopathology*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology*; D006358:Hot Temperature; D020287:In Situ Nick-End Labeling; D008099:Liver; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D019392:Cytochrome P-450 CYP2E1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase