title: H-rev107 Regulates Cytochrome P450 Reductase Activity and Increases Lipid Accumulation.
abstract: H-rev107 is a member of the HREV107 type II tumor suppressor gene family and acts as a phospholipase to catalyze the release of fatty acids from glycerophospholipid. H-rev107 has been shown to play an important role in fat metabolism in adipocytes through the PGE2/cAMP pathway, but the detailed molecular mechanism underlying H-rev107-mediated lipid degradation has not been studied. In this study, the interaction between H-rev107 and cytochrome P450 reductase (POR), which is involved in hepatic lipid content regulation, was determined by yeast two-hybrid screen and confirmed by using in vitro pull down assays and immunofluorescent staining. The expression of POR in H-rev107-expressing cells enhanced the H-rev107-mediated release of arachidonic acid. However, H-rev107 inhibited POR activity and relieved POR-mediated decreased triglyceride content in HtTA and HeLa cervical cells. The inhibitory effect of H-rev107 will be abolished when POR-expressing cells transfected with PLA2-lacking pH-rev107 or treated with PLA2 inhibitor. Silencing of H-rev107 using siRNA resulted in increased glycerol production and reversion of free fatty acid-mediated growth suppression in Huh7 hepatic cells. In summary, our results revealed that H-rev107 is also involved in lipid accumulation in liver cells through the POR pathway via its PLA2 activity.
authors.affiliation: Department of Research, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City, Taiwan.
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Tsai
authors.affiliation: Department of Research, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City, Taiwan.
authors.forename: Mao-Liang
authors.initials: ML
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Lu-Kai
authors.initials: LK
authors.lastname: Wang
authors.affiliation: Department of Research, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Lee
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism; D054512:Phospholipases A2, Calcium-Independent / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D005230:Fatty Acids, Nonesterified; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D016718:Arachidonic Acid; D009251:NADPH-Ferrihemoprotein Reductase; C490065:PLAAT3 protein, human; D054467:Phospholipases A2; D054512:Phospholipases A2, Calcium-Independent; D005990:Glycerol