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Titolo:
Na+ effects on mitochondrial respiration and oxidative phosphorylation in diabetic hearts
Autore:
Babsky, A; Doliba, N; Doliba, N; Savchenko, A; Wehrli, S; Osbakken, M;
Indirizzi:
Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 & Biophys, Philadelphia, PA 19104 USA Covance, Princeton, NJ 08540 USA Covance Princeton NJ USA 08540Covance, Princeton, NJ 08540 USA Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA Childrens Hosp Philadelphia Philadelphia PA USA 19104 lphia, PA 19104 USA Aventis, Bridgewater, NJ USA Aventis Bridgewater NJ USAAventis, Bridgewater, NJ USA
Titolo Testata:
EXPERIMENTAL BIOLOGY AND MEDICINE
fascicolo: 6, volume: 226, anno: 2001,
pagine: 543 - 551
SICI:
1535-3702(200106)226:6<543:NEOMRA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT HEARTS; FREE CA2+; SODIUM; CALCIUM; MODULATION; MUSCLE; SPECTROSCOPY; METABOLISM; EXCHANGER; TRANSPORT;
Keywords:
diabetes; heart; mitochondria; sodium; calcium; oxidative phosphorylation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Osbakken, M Univ Penn, Dept Biochem & Biophys, 207 Anat Chem Bldg,37th St & Hamilton Walk, Philadelphia, PA 19104 USA Univ Penn 207 Anat Chem Bldg,37th St & Hamilton Walk Philadelphia PA USA 19104
Citazione:
A. Babsky et al., "Na+ effects on mitochondrial respiration and oxidative phosphorylation in diabetic hearts", EXP BIOL ME, 226(6), 2001, pp. 543-551

Abstract

Intracellular Na+ is approximately two times higher in diabetic cardiomyocytes than in control. We hypothesized that the increase in Na+, activates the mitochondrial membrane Na+/Ca2+ exchanger, which leads to toss of intramitochondrial Ca2+, with a subsequent alteration (generally depression) in bioenergetic function. To further evaluate this hypothesis, mitochondria were isolated from hearts of control and streptozotocin-induced (4 weeks) diabetic rats. Respiratory function and ATP synthesis were studied using routine polarography and P-31-NMR methods, respectively. While addition of Na+ (1-10 mM) decreased State 3 respiration and rate of oxidative phosphorylationin both diabetic and control mitochondria, the decreases were significantly greater for diabetic than for control. The Na+ effect was reversed by providing different levels of extramitochondrial Ca2+ (larger Ca2+ levers wereneeded to reverse the Na+ depressant effect in diabetes mellitus than in control) and by inhibiting the Na+/Ca2+ exchanger function with diltiazem (aspecific blocker of Na+/Ca2+ exchange that prevents Ca2+ from leaving the mitochondrial matrix). On the other hand, the Na+ depressant effect was enhanced by Ruthenium Red (RR, a blocker of mitochondrial Ca2+ uptake, which decreases intramitochondrial Ca2+). The RR effect on Na+ depression of mitochondrial bioenergetic function was larger in diabetic than control. These findings suggest that intramitochondrial Ca2+ levels could be lower in diabetic than control and that the Na+ depressant effect has some relation to lowered intramitochondrial Ca2+. Conjoint experiments with P-31-NMR in isolated superfused mitochondria embedded in agarose beads showed that Na+ (3-30 mM) red to significantly decreased ATP revels in diabetic rats, but produced smaller changes in control. These data support our hypothesis that in diabetic cardiomyocytes, increased Na+ leads to abnormalities of oxidative processes and subsequent decrease in ATP levels, and that these changes are related to Na+ induced depletion of intramitochondrial Ca2+.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 13:05:01