title: Relevance of stretch-induced phosphorylation of MAPK and p90rsk in human myocardium.
abstract: Stretch activates various signal transduction pathways including mitogen-activated protein kinases (MAPK). Stretch-induced phosphorylation of MAPK-contribution to contractility in human myocardium is unknown. We tested the effects of stretch on p44/42-, p38-MAPK and p90rsk phosphorylation and the functional relevance for force development in failing (F) and non-failing (NF) human myocardium. Trabeculae were stretched to a diastolic tension of 12mN/mm2 for 2.5 to 30 minutes and frozen for Western Blot analysis. Stretch induced a time-dependent increase in phosphorylation of p44/42-, p38-MAPK and p90rsk. For functional analysis, trabeculae from F myocardium were stretched and the immediate (Frank-Starling mechanism; FSM) and delayed (slow force response; SFR) increase in twitch force was assessed before and after blocking the activation of p44/42-MAPK (30 micromol/L U0126) and p38-MAPK (10 micromol/L SB203580). Inhibition of p44/42-MAPK almost completely blocked the SFR (106.7 3.7% vs. 125.4 2.9%), while p38-MAPK-blockade significantly increased the SFR (124.6 1.9% vs. 121.2 2.2%). Stretch induced a time-dependent increase in p44/42-, p38-MAPK and p90rsk phosphorylation in F and NF myocardium. While p44/42-MAPK phosphorylation contributed to the SFR, p38-MAPK activation antagonized the stretch-induced SFR.
authors.affiliation: Division of Cardiology, Medical University of Graz, Graz, Austria.
authors.forename: Anke
authors.initials: A
authors.lastname: Kockskamper
authors.forename: Dirk
authors.initials: D
authors.lastname: von Lewinski
authors.forename: Danan
authors.initials: D
authors.lastname: Zhu
authors.forename: Jens
authors.initials: J
authors.lastname: Kockskamper
authors.forename: Mounir
authors.initials: M
authors.lastname: Khafaga
authors.forename: Albrecht G
authors.initials: AG
authors.lastname: Schmidt
authors.forename: Heiner
authors.initials: H
authors.lastname: Post
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
mesh_terms: D006333:Heart Failure / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D010766:Phosphorylation; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D038744:Ribosomal Protein S6 Kinases, 90-kDa; D020928:Mitogen-Activated Protein Kinases