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

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.

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Functional State of Rat Heart Mitochondria in Experimental Hyperthyroidism

International Journal of Molecular Sciences ◽

10.3390/ijms222111744 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11744

Author(s):

Natalya Venediktova ◽

Ilya Solomadin ◽

Anna Nikiforova ◽

Vlada Starinets ◽

Galina Mironova

Keyword(s):

Oxidative Stress ◽

Rat Heart ◽

Chronic Administration ◽

Heart Mitochondria ◽

Free Triiodothyronine ◽

Experimental Animals ◽

Transport Chain ◽

Hypertrophy Of The Heart ◽

Mitochondria Of The Heart ◽

Rat Heart Mitochondria

In this work, the effect of thyroxine on energy and oxidative metabolism in the mitochondria of the rat heart was studied. Hyperthyroidism was observed in experimental animals after chronic administration of T4, which was accompanied by an increase in serum concentrations of free triiodothyronine (T3) and thyroxine (T4) by 1.8 and 3.4 times, respectively. The hyperthyroid rats (HR) had hypertrophy of the heart. In HR, there was a change in the oxygen consumption in the mitochondria of the heart, especially when using palmitoylcarnitine. The assay of respiratory chain enzymes revealed that the activities of complexes I, I + III, III, IV increased, whereas the activities of complexes II, II + III decreased in heart mitochondria of the experimental animals. It was shown that the level of respiratory complexes of the electron transport chain in hyperthyroid rats increased, except for complex V, the quantity of which was reduced. The development of oxidative stress in HR was observed: an increase in the hydrogen peroxide production rate, increase in lipid peroxidation and reduced glutathione. The activity of superoxide dismutase in the heart of HR was higher than in the control. At the same time, the activity of glutathione peroxidase decreased. The obtained data indicate that increased concentrations of thyroid hormones lead to changes in energy metabolism and the development of oxidative stress in the heart of rats, which in turn contributes to heart dysfunction.

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

International Journal of Physiology and Pathophysiology ◽

10.1615/intjphyspathophys.v5.i2.70 ◽

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

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

Biochemical Journal ◽

10.1042/bj3190633 ◽

1996 ◽

Vol 319 (2) ◽

pp. 633-640 ◽

Cited By ~ 23

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.

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

10.15407/fz59.02.009 ◽

2013 ◽

Vol 59 (2) ◽

pp. 9-17 ◽

Cited By ~ 1

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

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Effect of Melatonin on Rat Heart Mitochondria in Acute Heart Failure in Aged Rats

International Journal of Molecular Sciences ◽

10.3390/ijms19061555 ◽

2018 ◽

Vol 19 (6) ◽

pp. 1555 ◽

Cited By ~ 15

Author(s):

Irina Odinokova ◽

Yulia Baburina ◽

Alexey Kruglov ◽

Irina Fadeeva ◽

Alena Zvyagina ◽

...

Keyword(s):

Heart Failure ◽

Acute Heart Failure ◽

Rat Heart ◽

Heart Mitochondria ◽

Aged Rats ◽

Rat Heart Mitochondria

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Astaxanthin Prevents Mitochondrial Impairment Induced by Isoproterenol in Isolated Rat Heart Mitochondria

Antioxidants ◽

10.3390/antiox9030262 ◽

2020 ◽

Vol 9 (3) ◽

pp. 262 ◽

Cited By ~ 5

Author(s):

Olga Krestinina ◽

Yulia Baburina ◽

Roman Krestinin ◽

Irina Odinokova ◽

Irina Fadeeva ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Rat Heart ◽

Adenine Nucleotide ◽

Heart Function ◽

Isolated Rat Heart ◽

Heart Mitochondria ◽

Cyclophilin D ◽

Inner Mitochondrial Membrane ◽

Respiratory Chain Complexes ◽

Rat Heart Mitochondria

Mitochondria are considered to be a power station of the cell. It is known that they play a major role in both normal and pathological heart function. Alterations in mitochondrial bioenergetics are one of the main causes of the origin and progression of heart failure since they have an inhibitory effect on the activity of respiratory complexes in the inner mitochondrial membrane. Astaxanthin (AST) is a xanthophyll carotenoid of mainly marine origin. It has both lipophilic and hydrophilic properties and may prevent mitochondrial dysfunction by permeating the cell membrane and co-localizing within mitochondria. The carotenoid suppresses oxidative stress-induced mitochondrial dysfunction and the development of diseases. In the present study, it was found that the preliminary oral administration of AST upregulated the activity of respiratory chain complexes and ATP synthase and the level of their main subunits, thereby improving the respiration of rat heart mitochondria (RHM) in the heart injured by isoproterenol (ISO). AST decreased the level of cyclophilin D (CyP-D) and increased the level of adenine nucleotide translocase (ANT) in this condition. It was concluded that AST could be considered as a potential mitochondrial-targeted agent in the therapy of pathological conditions associated with oxidative damage and mitochondrial dysfunction. AST, as a dietary supplement, has a potential in the prevention of cardiovascular diseases.

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

10.14293/p2199-8442.1.sop-med.piil0i.v1 ◽

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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