Cellular localization of integrin isoforms in phenylephrine-induced hypertrophic cardiac myocytes.
Cardiac hypertrophy is characterized by remodeling of the extracellular matrix (ECM). Integrins are cell-surface molecules that link the ECM to the cellular cytoskeleton where they play roles as signaling molecules and transducers of mechanical force. To clarify the possible roles of integrins in cardiac myocyte hypertrophy, we investigated the cellular localization and expression of ECM proteins and integrins in both normal cardiac myocytes and phenylephrine-induced hypertrophic myocytes. Addition of phenylephrine (PE) to cultured neonatal cardiac myocytes induced sarcomeric organization, increase in cell size, and synthesis of the hypertrophic marker, atrial natriuretic factor (ANF). In particular, fibronectin and collagen underwent dramatic localization changes during PE-induced cardiac hypertrophy. Significant changes were noted in the cellular localization of the respective collagen and fibronectin receptors, integrin alpha1 and alpha5, from diffuse to a sarcomeric banding pattern. Expression levels of integrins were also increased during hypertrophy. Treatment with okadaic acid (OA), an inhibitor of protein phosphatase 2A (PP2A), resulted in inhibition of hypertrophic response. These results suggest that dephosphorylation of integrin beta1 may be important in the induction of cardiac hypertrophy.
Kim
Dae Joong
DJ
Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500-712, Korea.
Park
Sang Hee
SH
Lim
Chol Seung
CS
Chun
Jang-Soo
JS
Kim
Jin-Kyu
JK
Song
Woo Keun
WK
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019319:Okadaic Acid / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology*; D020033:Protein Isoforms / Q000378:metabolism*; D051381:Rats
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D005353:Fibronectins; D016023:Integrins; D020033:Protein Isoforms; D019319:Okadaic Acid; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D003094:Collagen