Polyamines mediate abnormal Ca/sup 2 +/ transport and Ca/sup 2 +/-induced cardiac cell injury in the calcium paradox
Ca/sup 2 +/-free perfusion renders heart cells Ca/sup 2 +/-sensitive so that readmission of Ca/sup 2 +/ causes a sudden massive cellular injury attributed to abnormal entry of Ca/sup 2 +/ into cells (Ca paradox). Hormonal stimulation of Ca/sup 2 +/ fluxes was earlier shown to be mediated by polyamines (PA). 5 min perfusion of rat heart with Ca/sup 2 +/-free medium induce a prompt 40-50% decline in levels of the PA putrescine (PUT), spermidine and spermine and their rate-regulatory synthetic enzyme ornithine decarboxylase (ODC), and readmission of Ca/sup 2 +/-containing medium abruptly (< 30-60 sec) increased the levels of ODC and PA. The ODC inhibitor ..cap alpha..-difluoromethylornithine (DFMO, 5mM) blocked Ca/sup 2 +/ reperfusion-induced increases in ODC and PA and also prevented increased /sup 45/Ca/sup 2 +/ uptake and heart injury, manifested by loss of contractility, release of enzymes (CPK, LDH), myoglobin and protein, and E.M. lesions (contracture bands, mitochondrial changes). 1 mM PUT negated DFMO inhibition, repleted heart PA and restored Ca/sup 2 +/ reperfusion-induced /sup 45/Ca/sup 2 +/ influx and cell injury. These data indicate that the Ca/sup 2 +/-directed depletion-repletion cycle of ODC and PA triggers excessive transsarcolemmal Ca/sup 2 +/ transport leading to the calcium paradox.
- Research Organization:
- Northwestern Univ. Medical School, Chicago, IL
- OSTI ID:
- 6958406
- Report Number(s):
- CONF-8604222-; TRN: 87-003808
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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BIOCHEMICAL REACTION KINETICS
CALCIUM COMPOUNDS
BIOLOGICAL EFFECTS
MEMBRANE TRANSPORT
HEART
INJURIES
CALCIUM 45
RATS
TRACER TECHNIQUES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
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CALCIUM ISOTOPES
CARDIOVASCULAR SYSTEM
DAYS LIVING RADIOISOTOPES
EVEN-ODD NUCLEI
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ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
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RODENTS
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550201* - Biochemistry- Tracer Techniques
550901 - Pathology- Tracer Techniques