title: Modest actomyosin energy conservation increases myocardial postischemic function.
abstract: We have proposed that pharmacological preconditioning, leading to PKC-epsilon activation, in hearts improves postischemic functional recovery through a decrease in actomyosin ATPase activity and subsequent ATP conservation. The purpose of the present study was to determine whether moderate PKC-independent decreases in actomyosin ATPase are sufficient to improve myocardial postischemic function. Rats were given propylthiouracil (PTU) for 8 days to induce a 25% increase in beta-myosin heavy chain with a 28% reduction in actomyosin ATPase activity. Recovery of postischemic left ventricular developed pressure (LVDP) was significantly higher in PTU-treated rat hearts subjected to 30 min of global ischemia than in control hearts: 57.9 +/- 6.2 vs. 32.6 +/- 5.1% of preischemic values. In addition, PTU-treated hearts exhibited a delayed onset of rigor contracture during ischemia and a higher global ATP content after ischemia. In the second part of our study, we demonstrated a lower maximal actomyosin ATPase and a higher global ATP content after ischemia in human troponin T (TnT) transgenic mouse hearts. In mouse hearts with and without a point mutation at F110I of human TnT, recovery of postischemic LVDP was 55.4 +/- 5.5 and 62.5 +/- 14.5% compared with 20.0 +/- 2.9% in nontransgenic mouse hearts after 35 min of global ischemia. These results are consistent with the hypothesis that moderate decreases in actomyosin ATPase activity result in net ATP conservation that is sufficient to improve postischemic contractile function.
authors.affiliation: Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida, USA.
authors.forename: Bradford C
authors.initials: BC
authors.lastname: Blunt
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: James D
authors.initials: JD
authors.lastname: Potter
authors.forename: Polly A
authors.initials: PA
authors.lastname: Hofmann
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D000225:Adenine / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D051381:Rats; D017207:Rats, Sprague-Dawley; D020107:Troponin T / Q000235:genetics / Q000378:metabolism
chemical_list: C000594638:MYH7 protein, rat; D020107:Troponin T; D000255:Adenosine Triphosphate; D000205:Actomyosin; C497259:Prkcd protein, mouse; C497260:Prkcd protein, rat; C497256:Prkce protein, mouse; C497257:Prkce protein, rat; C497258:PRKCD protein, human; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D000251:Adenosine Triphosphatases; D018995:Myosin Heavy Chains; D000225:Adenine; D003401:Creatine; D002118:Calcium