title: Lipid extract of Nostoc commune var. sphaeroides Kutzing, a blue-green alga, inhibits the activation of sterol regulatory element binding proteins in HepG2 cells.
abstract: Nostoc commune var. sphaeroides Kützing (N. commune), a blue-green alga, has been used as both a food ingredient and in medicine for centuries. To determine the effect of N. commune on cholesterol metabolism, N. commune lipid extract was incubated at increasing concentrations (25-100 mg/L) with HepG2 cells, a human hepatoma cell line. The addition of N. commune lipid extract markedly reduced mRNA abundance of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and LDL receptor (LDLR) (P < 0.05), with a concomitant decrease in their protein expression (P < 0.001). Reduced HMGR activity by 90% with N. commune lipid extract confirmed the inhibitory role of N. commune in cholesterol synthesis (P < 0.006). To elucidate a molecular mechanism underlying the repression of HMGR and LDLR by N. commune lipid extract, expression of sterol regulatory element binding protein 2 (SREBP-2) was assessed. Whereas mRNA for SREBP-2 remained unchanged, SREBP-2 mature protein was reduced by N. commune (P < 0.009). In addition, N. commune lipid extract also decreased SREBP-1 mature protein by approximately 30% (P < 0.002) and reduced the expression of SREBP-1-responsive genes such as fatty acid synthase and stearoyl CoA desaturase 1 (SCD-1) (P < 0.05). Therefore, our results demonstrate that N. commune lipid extract inhibits the maturation process of both SREBP-1 and -2, resulting in a decrease in expression of genes involved in cholesterol and fatty acid metabolism.
authors.affiliation: Department of Nutrition, University of Nebraska, Lincoln, NE 68583, USA.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Rasmussen
authors.forename: Kara R
authors.initials: KR
authors.lastname: Blobaum
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Park
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Ehlers
authors.forename: Fan
authors.initials: F
authors.lastname: Lu
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D056890:Eukaryota / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism*; D050501:Nostoc commune / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D051779:Sterol Regulatory Element Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D012333:RNA, Messenger; D011973:Receptors, LDL; D051779:Sterol Regulatory Element Binding Proteins; D006903:Hydroxymethylglutaryl CoA Reductases