title: Actin dynamics is rapidly regulated by the PTEN and PIP2 signaling pathways leading to myocyte hypertrophy.
abstract: Mature cardiac myocytes are terminally differentiated, and the heart has limited capacity to replace lost myocytes. Thus adaptation of myocyte size plays an important role in the determination of cardiac function. The hypothesis tested is that regulation of the dynamic exchange of actin leads to cardiac hypertrophy. ANG II was used as a hypertrophic stimulant in mouse heart and neonatal rat ventricular myocytes (NRVMs) in culture for assessment of a mechanism for regulation of actin dynamics by phosphatidylinositol 4,5-bisphosphate (PIP2). Actin dynamics in NRVMs rapidly increased in a PIP2-dependent manner, measured by imaging and fluorescence recovery after photobleaching (FRAP). A significant increase in PIP2 levels was found by immunoblotting in both adult mouse heart tissue and cultured NRVMs. Inhibition of phosphatase and tensin homolog (PTEN) in NRVMs markedly blunted ANG II-induced increases in actin dynamics, the PIP2 level, and cell size. Furthermore, PTEN activity was dramatically upregulated in ANG II-treated NRVMs but downregulated when PTEN inhibitors were used. The time course of the rise in the PIP2 level was inversely related to the fall in the PIP3 level, which was significant by 30 min in ANG II-treated NRVMs. However, significant translocation of PTEN to the plasma membrane occurred by 10 min, suggesting a crucial initial step for PTEN for the cellular responses to ANG II. In conclusion, PTEN and PIP2 signaling may play an important role in myocyte hypertrophy by the regulation of actin filament dynamics, which is induced by ANG II stimulation.
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Jieli
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Tanhehco
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois russell@uic.edu.
authors.forename: Brenda
authors.initials: B
authors.lastname: Russell
mesh_terms: D000199:Actins / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology*; D048429:Cell Size / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000502:physiology*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000199:Actins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; D000804:Angiotensin II; D051059:PTEN Phosphohydrolase
keywords: G protein receptors; lipid signaling; membrane translocation; sarcomere remodeling