Exogenous metalloporphyrins alter the organization and function of cultured neonatal rat heart cells via modulation of heme oxygenase activity.
Heme oxygenase (HO), the enzyme responsible for heme catabolism, has been associated with the function of both skeletal and smooth muscle cells and with protection of the heart against ischemia/reperfusion injury. Exposure of skeletal muscle cultures to heme, the physiological substrate for HO, has been shown to improve differentiation and aerobic metabolism. Little is known, however, about the roles that heme and heme metabolism play in cardiac muscle, and the present study was conducted to examine the effects of exogenous heme on cultured heart cells in the presence or absence of modulators of HO activity. Treatment of neonatal rat ventricular cells with heme resulted in increases in four key indicators: (1) the activity of metabolic enzymes, (2) the rate of spontaneous contraction, (3) the level of myosin heavy chain (MyHC) expressed, and (4) the amount of actin organized as filaments. Treatment with heme while metabolically inhibiting increased HO activity altered these effects such that: (1) increases in enzyme activities were attenuated, (2) spontaneous beating ceased, (3) the level of MyHC was reduced, and (4) the amount of filamentous actin was severely decreased to the point where myofibrils were no longer evident. These results suggest that heme and its catabolites act to modulate aspects of cardiac cell function and organization.
Department of Biomedical Research, A. I. duPont Hospital for Children, Wilmington, Delaware, USA. rakins@nemours.org
Robert
R
Akins
Terry
T
McLaughlin
Roberta
R
Boyce
Laura
L
Gilmour
Kara
K
Gratton
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D009841:Oligonucleotides / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D011524:Protoporphyrins; C448299:iron protoporphyrin IX; C017803:zinc protoporphyrin; D006418:Heme; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1