Nitric oxide is critical for avoiding hepatic lipid overloading via IL-6 induction during liver regeneration after partial hepatectomy in mice

Experimental Animals
Yue YuYoh-Ichi Tagawa

Abstract

Nitric oxide (NO), generated from L-arginine by three different isoforms of nitric oxide synthase (NOS), is a pleiotropic factor to regulate physiological functions in almost every organ and tissue. Each knockout mouse of iNOS or eNOS has been used to suggest that NO has a crucial role in liver regeneration after partial hepatectomy (PH), for NO may inhibit caspase 3 activity and is required for EGFR signaling. In previous reports, defective mitochondrial β-oxidation was observed in eNOS KO mice, and hepatic steatosis was often correlated to deficient liver regeneration, so we focused on metabolic perspective and hypothesized that NO depletion in PH mice would affect hepatocytic lipolysis and impair hepatocytes proliferation. We inhibited all NOS isoforms by administrating L-NG-nitroarginine methyl ester (L-NAME) to PH mice, and hepatocyte DNA synthesis was severely inhibited at 40-44 h post PH in L-NAME (+) group. IL-6 was robustly secreted into circulating blood in L-NAME (-) group, but not in L-NAME (+) group. Down-regulation of carnitine palmytoyltransferase 1A, massive lipid accumulation and elevated endoplasmic reticulum (ER) stress relative genes expression level were observed in L-NAME (+) group mouse liver. The express...Continue Reading

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Citations

Jun 30, 2018·Oxidative Medicine and Cellular Longevity·Oren Tirosh
Nov 2, 2018·International Journal of Molecular Sciences·Ana Isabel Álvarez-MercadoCarmen Peralta

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Methods Mentioned

BETA
transgenic
dissection
PCR

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