Q112413025
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Dysfunction of mitochondria induced by ischemia is considered to be a key event triggering neuronal cell death after brain ischemia. Here we report the effect of ischemia-reperfusion on mitochondrial protein synthesis and activity of cytochrome c oxidase (EC 1.9.3.1, COX). By performing 4-vessel occlusion model of global brain ischemia, we have observed that 15 min of global ischemia led to the inhibition of COX subunit I (COXI) synthesis to 56 % of control. After 1, 3 and 24 h of reperfusion, COXI synthesis was inhibited to 46, 50 and 72 % of control, respectively. Depressed synthesis of COXI was not a result of either diminished transcription of COXI gene or increased proteolytic degradation of COXI, since both Northern hybridization and Western blotting did not show significant changes in COXI mRNA and protein level. Thus, ischemia-reperfusion affects directly mitochondrial translation machinery. In addition, ischemia in duration of 15 min and consequent 1, 3 and 24 h of reperfusion led to the inhibition of COX activity to 90.3, 80.3, 81.9 and 83.5 % of control, respectively. Based on our data, we suggest that inhibition of COX activity is rather caused by ischemia-induced modification of COX polypeptides than by inhibition of mitochondrial translation.
- MeSH
- časové faktory MeSH
- down regulace MeSH
- financování organizované MeSH
- genetická transkripce MeSH
- ischemie mozku enzymologie komplikace MeSH
- krysa rodu rattus MeSH
- messenger RNA metabolismus MeSH
- mitochondriální proteiny biosyntéza genetika MeSH
- mitochondrie enzymologie MeSH
- modely nemocí na zvířatech MeSH
- mozková kůra enzymologie MeSH
- posttranslační úpravy proteinů MeSH
- potkani Wistar MeSH
- regulace genové exprese enzymů MeSH
- reperfuzní poškození enzymologie etiologie MeSH
- respirační komplex IV biosyntéza genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Starnutie charakterizuje postupné zhoršovanie fyziologických funkcií a metabolických procesov. Bunkové a molekulové mechanizmy starnutia nie sú dosiaľ objasnené, rastie však počet experimentálnych dôkazov o úlohe oxidačného stresu v tomto procese. V tejto práci sme sledovali vplyv veku na 1) aktivity enzýmov α-ketoglutarátdehydrogenázy (KGDH) a cytochróm c oxidázy (COX) a 2) oxidačné modifikácie mitochondriálnych lipidov a bielkovín v mozgu potkanov kmeňa Wistar. Starnutie sprevádzal výrazný pokles aktivity oboch enzýmov, v mozgu 26mesačných zvierat bola aktivita KGHD znížená o 34,8 % a aktivita COX až o 52,2 % v porovnaní s aktivitou 5mesačných zvierat. Počas starnutia sa výrazne zvyšovala lipidová peroxidácia (LPO), koncentrácia produktov LPO v mitochondriách starých potkanov bola viac ako dvojnásobne zvýšená. Navyše, akumulácia týchto produktov viedla k štrukturálnej modifikácii mitochondriálnych bielkovín. Naše výsledky naznačujú, že jedným z pravdepodobných mechanizmov poklesu aktivity mitochondriálnych enzýmov počas starnutia je oxidačné poškodenie lipidov a bielkovín.
Aging is characterized by a progressive deterioration of physiological functions and metabolic processes. The exact cellular and molecular mechanizms of the aging process are unclear, but there is a growing evidence that age-related changes are consequences of oxidative stress. In the present study we examined the effect of aging on (i) α-ketoglutarate dehydrogenase (KGDH) and cytochrome c oxidase (COX) activity and (ii) oxidative modifications of mitochondrial lipids and proteins in brains from male Wistar rats. The activity of both enzymes was significantly reduced during aging, in hearts from 26-months-old rats KGDH and COX was lower by 34.8 ± 2.1% and 52.2 ± 1.1%, respectively, when compares to adult 5-months-old rats. Aging was associated with significant increase in lipid peroxidation (LPO), in old rats the concentration of LPO products increased more than 2 fold. Furthermore, the accumulation of LPO products leads structural modification of mitochondrial proteins. Our results suggest that loss of enzyme activities during aging may be related to oxidative modifications of mitochondrial proteins and/or lipids.
- MeSH
- finanční podpora výzkumu jako téma MeSH
- krysa rodu rattus MeSH
- mitochondriální proteiny analýza MeSH
- mitochondrie enzymologie metabolismus MeSH
- modely u zvířat MeSH
- mozek cytologie enzymologie MeSH
- oxidační stres MeSH
- peroxidace lipidů MeSH
- stárnutí MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
