title: Endothelin-1- and isoproterenol-induced differential protein expression and signaling pathway in HL-1 cardiomyocytes.
abstract: It is well known that the two chemical compounds endothelin-1 (ET-1) and isoproterenol (ISO) can individually induce cardiac hypertrophy through G protein-coupled receptors in cardiomyocytes. However, the cardiac hypertrophy signaling pathway activated by ET-1 and ISO is not well defined. Therefore, we investigated the protein expression profile and signaling transduction in HL-l cardiomyocyte cells treated with ET-1 and ISO. Following separation of the cell lysates by using 2-DE and silver staining, we identified 16 protein spots that were differentially expressed as compared to the controls. Of these 16 spots, three changed only after treatment with ET-1, whereas four changed only after treatment with ISO, suggesting that these two stimuli could induce different signaling pathways. In order to reveal the differences between ET-1- and ISO-induced signaling, we studied the different events that occur at each step of the signaling pathways, when selected biocomponents were blocked by inhibitors. Our results indicated that ET-1 and ISO used different pathways for phosphorylation of glycogen synthase kinase-3β (GSK3β). ET-1 mainly used the mitogen-activated protein kinase and phosphatidylinositol-3-kinase/AKT pathways to activate GSK3β, whereas under ISO stimulation, only the phosphatidylinositol-3-kinase/AKT pathway was required to trigger the GSK3β pathway. Furthermore, the strength of the GSK3β signal in ISO-induced cardiac hypertrophy was stronger than that in ET-1-induced cardiac hypertrophy. We found that these two agonists brought about different changes in the protein expression of HL-1 cardiomyocytes through distinct signaling pathways even though the destination of the two signaling pathways was the same.
authors.affiliation: Integrated Omics Center, Life/Health Division Korea Institute of Science and Technology, Cheongryang, Seoul, Korea.
authors.forename: Hye-Min
authors.initials: HM
authors.lastname: Hong
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Song
authors.forename: Eulsik
authors.initials: E
authors.lastname: Oh
authors.forename: Mohammad Humayun
authors.initials: MH
authors.lastname: Kabir
authors.forename: Cheolju
authors.initials: C
authors.lastname: Lee
authors.forename: Young Sook
authors.initials: YS
authors.lastname: Yoo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D019332:Endothelin-1 / Q000009:adverse effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D053719:Tandem Mass Spectrometry
chemical_list: D002316:Cardiotonic Agents; D019332:Endothelin-1; D011506:Proteins; D007545:Isoproterenol