title: Ethylacetate fraction from Korean seaside starfish, Asterias amurensis, has an inhibitory effect on MMP-9 activity and expression and on migration behavior of TNF-α induced human aortic smooth muscle cells.
abstract: Atherosclerosis is accompanied by the proliferation of human aortic smooth muscle cells (HASMC) and their movement into the intima. Many reports have indicated the involvement of gelatinases (MMP-9 and MMP-2) in this pathogenesis. The ethylacetate fraction from starfish, Asterias amurensis (EFA), harvested from the Korean seaside has an inhibitory effect on MMP-9 and MMP-2 activities, as well as on the expression of MMP-9 in TNF-α induced HASMC in a dose-dependent manner. Also, EFA inhibits the migration of TNF-α induced HASMC in transwells containing gelatin coated plugs. EFA was not cytotoxic to HASMC over the range 0-1mg/ml. By Western-blot analysis, it was revealed that the phosphorylation of extracellular signal regulated kinase (ERK) in TNF-α induced cells was inhibited and nuclear factor kappa B (NF-κB) p65 levels in nuclear extracts were decreased by EFA treatment. In addition, ERK inhibitor (U0126) treated cells exhibited decreased MMP-9 activity in the zymographic assay. From these results, it was found that the gelatinolytic activity was regulated (1) by enzymatic inhibition of both MMP-9 and MMP-2, as well as (2) by the decreased production of MMP-9 via ERK pathways in EFA treated HASMCs. Taken together, it has been shown that EFA has a putative anti-atherosclerotic effect.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Seok-Jong
authors.initials: SJ
authors.lastname: Suh
authors.forename: Hyun-Kwon
authors.initials: HK
authors.lastname: Ko
authors.forename: Kwon-Ho
authors.initials: KH
authors.lastname: Song
authors.forename: Jeong-Ran
authors.initials: JR
authors.lastname: Kim
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Kwon
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.forename: Young-Choon
authors.initials: YC
authors.lastname: Lee
authors.forename: Dong-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Sung-Jae
authors.initials: SJ
authors.lastname: Park
authors.forename: Ju Hye
authors.initials: JH
authors.lastname: Yang
authors.forename: Jong-Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Min-Kyun
authors.initials: MK
authors.lastname: Na
authors.forename: Hyeun-Wook
authors.initials: HW
authors.lastname: Chang
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047271:Asterias / Q000737:chemistry*; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007723:Korea; D061965:Matrix Metalloproteinase Inhibitors; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000085:Acetates; D061965:Matrix Metalloproteinase Inhibitors; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C007650:ethyl acetate; D048049:Extracellular Signal-Regulated MAP Kinases