Nitric oxide mediates down regulation of lipoprotein lipase activity induced by tumor necrosis factor-α in brown adipocytes
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- 作者：Uchida ; Yoko ; Tsukahara ; Fujiko ; Ohba ; Ken-ichi ; Ogawa ; Akira ; Kaoru ; Irie ; Fujii ; Emiko ; Yoshimoto ; Takanobu ; et. al.
- 关键词：Brown adipocyte ; TMF-α ; (tumor necrosis factor-α ; ) ; Nitric oxide (NO) synthase ; inducible ; Lipoprotein lipase ; Guanosine 3&prime ; 5&prime ; -cyclic monophosphate
- 刊名：European Journal of Pharmacology
- 出版年：1997
- 出版时间：September 24, 1997
- 年：1997
- 卷：335
- 期：2-3
- 页码：235-243
- 全文大小：837 K
文摘
We previously reported that tumor necrosis factor-α (TNF-α)/cachectin suppresses lipoprotein lipase activity and its gene expression in brown adipocytes differentiated in culture. Recent evidence suggests that the effect of TNF-α over various cells is related to the enhanced production of nitric oxide (NO). The present study examined whether the suppressive effect of TNF-α on lipoprotein lipase activity is mediated by production of NO in the brown adipocytes. A reverse transcription-polymerase chain reaction (RT-PCR) assay revealed that TNF-α caused a concentration- and time-dependent expression of inducible NO synthase in brown adipocytes. Increasing concentrations of TNF-α (0.5–50 ng/ml) for 24 h resulted in a concentration-dependent decrease in lipoprotein lipase activity with reciprocal increase in nitrite production in the medium. The suppressive effect of TNF-α on lipoprotein lipase activity was significantly prevented by NO synthase inhibitors, NG-nitro--arginine methyl ester (-NAME) and aminoguanidine, but not by -NAME, an inactive isomer. Furthermore, 8-bromoguanosine 3′,5′-cyclic monophosphate, cell permeant cGMP, suppressed lipoprotein lipase activity and 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one, a selective inhibitor for soluble guanylate cyclase, restored the TNF-α-suppressed lipoprotein lipase activity. These results suggest that TNF-α stimulates brown adipocytes to express inducible NO synthase, followed by production of NO, which in turn mediates the suppressive effect of TNF-α on lipoprotein lipase activity. The effect of NO is mediated, at least partly, through production of cGMP.