scholarly journals The effect of respiratory chain impairment of β-oxidation in rat heart mitochondria

1996 ◽  
Vol 319 (2) ◽  
pp. 633-640 ◽  
Author(s):  
Simon EATON ◽  
Morteza POURFARZAM ◽  
Kim BARTLETT
Keyword(s):  
Respiratory Chain ◽  
Rat Heart ◽  
Redox State ◽  
Complex Iii ◽  
Heart Mitochondria ◽  
Cardiac Ischaemia ◽  
Low Concentrations ◽  
Rat Heart Mitochondria ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
14Co2 Release

Cardiac ischaemia leads to an inhibition of β-oxidation flux and an accumulation of acyl-CoA and acyl-carnitine esters in the myocardium. However, there remains some uncertainty as to which esters accumulate during cardiac ischaemia and therefore the site of inhibition of β-oxidation [Moore, Radloff, Hull and Sweely (1980) Am. J. Physiol. 239, H257-H265; Latipää (1989) J. Mol. Cell. Cardiol. 21, 765–771]. When β-oxidation of hexadecanoyl-CoA in state III rat heart mitochondria was inhibited by titration of complex III activity, flux measured as 14CO2 release, acid-soluble radioactivity or as acetyl-carnitine was progressively decreased. Low concentrations of myxothiazol caused reduction of the ubiquinone pool whereas the NAD+/NADH redox state was less responsive. Measurement of the CoA and carnitine esters generated under these conditions showed that there was a progressive decrease in the amounts of chain-shortened saturated acyl esters with increasing amounts of myxothiazol. The concentrations of 3-hydroxyacyl and 2-enoyl esters, however, were increased between 0 and 0.2 µM myxothiazol but were lowered at higher myxothiazol concentrations. More hexadecanoyl-CoA and hexadecanoyl-carnitine were present with increasing concentrations of myxothiazol. We conclude that 3-hydroxyacyl-CoA dehydrogenase and acyl-CoA dehydrogenase activities are inhibited by reduction of the ubiquinone pool, and that this explains the confusion over which esters of CoA and carnitine accumulate during cardiac ischaemia. Furthermore these studies demonstrate that the site of the control exerted by the respiratory chain over β-oxidation is shifted depending on the extent of the inhibition of the respiratory chain.

scholarly journals Effect of hydrogen sulfide donor NaHs on the functional state of the respiratory chain of the rat heart mitochondria

2013 ◽  
Vol 59 (2) ◽  
pp. 9-17 ◽  
Author(s):  
OM Semenykhina ◽  
◽  
NA Strutyns'ka ◽  
AIu Bud'ko ◽  
HL Vavilova ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Respiratory Chain ◽  
Functional State ◽  
Rat Heart ◽  
Heart Mitochondria ◽  
Rat Heart Mitochondria

Effect of NaHS, Hydrogen Sulfide Donor, on the Functional State of the Respiratory Chain in the Rat Heart Mitochondria

2014 ◽  
Vol 5 (2) ◽  
pp. 159-170
Author(s):  
Olena M. Semenykhina ◽  
Nataliya A. Strutynska ◽  
Alina Yu. Budko ◽  
Galyna L. Vavilova ◽  
Vadim F. Sagach
Keyword(s):  
Hydrogen Sulfide ◽  
Respiratory Chain ◽  
Functional State ◽  
Rat Heart ◽  
Heart Mitochondria ◽  
Rat Heart Mitochondria

scholarly journals The Identification of Prohibitin in the Rat Heart Mitochondria in Heart Failure

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1793
Author(s):  
Yulia Baburina ◽  
Roman Krestinin ◽  
Irina Odinokova ◽  
Irina Fadeeva ◽  
Linda Sotnikova ◽  
...  
Keyword(s):  
Heart Failure ◽  
Respiratory Chain ◽  
Rat Heart ◽  
Heart Function ◽  
Protective Action ◽  
Heart Mitochondria ◽  
Supramolecular Organization ◽  
Experimental Conditions ◽  
Mitochondria Of The Heart ◽  
Rat Heart Mitochondria

Mitochondria are considered the main organelles in the cell. They play an important role in both normal and abnormal heart function. There is a supramolecular organization between the complexes of the respiratory chain (supercomplexes (SCs)), which are involved in mitochondrial respiration. Prohibitins (PHBs) participate in the regulation of oxidative phosphorylation (OXPHOS) activity and interact with some subunits of the OXPHOS complexes. In this study, we identified a protein whose level was decreased in the mitochondria of the heart in rats with heart failure. This protein was PHB. Isoproterenol (ISO) has been used as a compound to induce heart failure in rats. We observed that astaxanthin (AX) increased the content of PHB in rat heart mitochondria isolated from ISO-injected rats. Since it is known that PHB forms complexes with some mitochondrial proteins and proteins that are part of the complexes of the respiratory chain, the change in the levels of these proteins was investigated under our experimental conditions. We hypothesized that PHB may be a target for the protective action of AX.

scholarly journals The effect of lead on the calcium-handling capacity of rat heart mitochondria

1976 ◽  
Vol 158 (2) ◽  
pp. 289-294 ◽  
Author(s):  
D R Parr ◽  
E J Harris
Keyword(s):  
Rat Heart ◽  
Heart Tissue ◽  
Calcium Handling ◽  
Primary Effect ◽  
Heart Mitochondria ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Low Concentrations ◽  
Rat Heart Mitochondria

1. Very low concentrations of Pb2+ decrease the capacity of rat heart mitochondria, oxidizing pyruvate plus malate, to remove Ca2+ from the medium. 2. The primary effect is on the rate of Ca2+ sequestration; this is reflected in the overall extent of Ca2+ removal. 3. Pb2+ has at least two separate actions. Below about 0.5 nmol/mg of protein, it acts solely by competing with Ca2+ (Ki = 0.4 muM); above this concentration it also inhibits the production or use of respiratory energy, so that at 1 nmol of Pb2+/mg of protein, Ca2+ removal is almost completely abolished. 4. Pb2+ inhibits coupled and uncoupled respiratory O2 use by mitochondria oxidizing pyruvate plus malate, but at higher concentrations than those that affect Ca2+ removal; similar concentrations of Pb2+ inhibit pyruvate uptake, but not malate uptake, by the mitochondria. 5. Mg2+ only decreases Ca2+ removal by competition, and is a far-less effective competitor than Pb2+ (Ki = 0.15 mM). It is possible that the primary cause of the second effect of Pb2+ is displacement of membrane Mg2+. 6. The consequences of these results are discussed in terms of the possible involvement of heart mitochondria in excitation-contraction coupling, and the Pb2+ levels that might occur in heart tissue in vivo.

Substrate specific effects of calcium on metabolism of rat heart mitochondria

1996 ◽  
Vol 270 (4) ◽  
pp. H1398-H1406 ◽  
Author(s):  
A. V. Panov ◽  
R. C. Scaduto
Keyword(s):  
Rat Heart ◽  
Redox State ◽  
Adenine Nucleotides ◽  
Enzyme Reaction ◽  
Isolated Rat Heart ◽  
Heart Mitochondria ◽  
Specific Substrate ◽  
Metabolic States ◽  
Tightly Coupled ◽  
Rat Heart Mitochondria

Oxidative metabolism in the heart is tightly coupled to mechanical work. Because this coupling process is believed to involve Ca2+, the roles of mitochondrial Ca2+ in the regulation of oxidative phosphorylation was studied in isolated rat heart mitochondria. The electrical component of the mitochondrial membrane potential (delta psi) and the redox state of the pyridine nucleotides were determined during the oxidation of various substrates under different metabolic states. In the absence of added adenine nucleotides, the NADP+ redox couple was almost completely reduced, regardless of the specific substrate and the presence of Ca2+, whereas NAD+ couple redox state was highly dependent on the substrate type and the presence of Ca2+. Titration of respiration with ADP, in the presence of excess hexokinase and glucose, showed that both respiration and NAD(P)+ reduction were very sensitive to ADP. The maximal enzyme reaction rate of ADP-stimulated respiration Michaelis constants (Km) for ADP were dependent on the particular substrate employed. delta psi was much less sensitive to ADP. With either alpha-ketoglutarate or glutamate as substrate, Ca2+ significantly increased reduction of NAD(P)+.Ca2+ did not influence NAD(P)+ reduction with either acetylcarnitine or pyruvate as substrate. In the presence of ADP, delta psi was increased by Ca2+ at all metabolic states with glutamate plus malate, 0.5 mM alpha-ketoglutarate plus malate, or pyruvate plus malate as substrates. The data presented support the hypothesis that cardiac respiration is controlled by the availability of both Ca2+ and ADP to mitochondria. The data indicate that an increase in substrate supply to mitochondria can increase mitochondrial respiration at given level of ADP. This effect can be produced by Ca2+ with substrates such as glutamate, which utilize alpha-ketoglutarate dehydrogenase activity for oxidation. Increases in respiration by Ca2+ may mitigate an increase in ADP during periods of increased cardiac work.

scholarly journals Characterization of Two Novel Pharmacological ATP-Sensitive Potassium Channels Modulators in Isolated Rat Heart Mitochondria

2014 ◽  
Author(s):  
Alexandra Petrus ◽  
Oana Duicu ◽  
Adrian Sturza ◽  
Lavinia Noveanu ◽  
István Baczkó ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Rat Heart ◽  
Ischemia Reperfusion ◽  
Isolated Rat Heart ◽  
Heart Mitochondria ◽  
Retention Capacity ◽  
Calcium Retention ◽  
Rat Heart Mitochondria ◽  
Calcium Retention Capacity ◽  
Isolated Rat

Background Mitochondrial dysfunction plays a major role in the pathogenesis of ischemia/reperfusion injury and cardiac arrhythmias. Mitochondrial ATP-sensitive potassium channel (mitoKATP) openers such as diazoxide and pinacidil have been reported to elicit cardioprotective effects via mild uncoupling and/or respiratory chain inhibition. The aim of the present study was to characterize the effects of two novel mitoKATP modulators (KL-1488 and KL 1495) on the respiratory rates and calcium retention capacity of isolated rat heart mitochondria. Methods Mitochondrial respiratory function was assessed by high-resolution respirometry (Oxygraph-2k Oroboros Ltd.) at 370C according to the Substrate-Uncoupler-Inhibitor Titration (SUIT) protocol, as follows: complex I (CI) and complex II (CII) dependent respiration was stimulated by glutamate + malate and rotenone + succinate, respectively (State 2) and subsequent ADP (State 3, OXPHOS state) addition; cytochrome c addition evaluated the intactness of the outer mitochondrial membrane; ATP synthase was inhibited by oligomycin (State 4); uncoupled respiration was obtained by FCCP titration; respiration was inhibited with antimycin A. Calcium retention capacity (CRC) was determined by spectrofluorimetry and calculated as the amount of calcium taken by mitochondria before opening of the mitochondrial permeability transition pore (mPTP) in the presence of the pharmacological agents. Results For both C I and C II-supported respiration, 150 µM of KL 1495 (but not of KL 1488) significantly increased respiratory rates in State 2 and 4, and decreased State 3 respiration, respectively. No inhibition of mPTP opening was observed in the presence of either compound. Conclusion The mitochondrial uncoupling and respiratory chain inhibition induced by KL 1495 could play a role in cardioprotection during the postischemic reperfusion. The research was funded by the POSDRU grant no. 159/1.5/S/136893 titled “Parteneriat strategic pentru creșterea calității cercetării științifice din universitățile medicale prin acordarea de burse doctorale și postdoctorale – DocMed.Net_2.0” (A.P.).

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