Angiotensin converting enzyme inhibitors are widely used in therapy of cardiovascular diseas es. However, the consensus on effects of these inhibitors in control of myocardial oxygen consumption during the process of experimental hypercholesterolemia and under the condition of endothelial dysfunction has not been reached. Here we examined effects of captopril, an angiotensin converting enzyme inhibitor, on serum lipid levels and oxygen consumption rate in mitochondria isolated from heart of rabbits treated by hypercholesterolemic diet. During the twelve-week period, th e Chinchilla male rabbits were daily treated by saline (controls); 1 % cholesterol diet; 5 mg/kg/day captopril or 1 % cholesterol + 5 mg/kg/day captopril. Total- and high-densi ty lipoprotein cholesterol and triglyceride in serum were measured spectrophotometricly. The left ventricle mitochondrial fraction was isolated and myocardial oxygen consumption was measur ed by Biological Oxygen Monitor. Mitochondria isolated from hearts of rabbits exposed to hypercholesterolemic diet sh owed significantly reduced respiration rates (state 3 and state 4) with altering adenosine diphosphate/oxygen ratio, whereas the respiratory control ratio was not affected when compared to controls. Mitochondria from cholesterol/captopril-treated animals showed significantly reduced respiration rates without altering adenosine diphosphate/oxygen ratio index or respiratory control ratio. Although captopril did not exert the favorable effect on serum lipid levels in cholesterol-treated animals, it restored the mitochondrial oxygen consumption. Further studies should be performed to define the under lying physiological and/or pathophysiological mechanisms and clinical implications., Z. Kojic ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Mitochondrial dysfunction and accumulation of oxidative damage have been implicated to be the major factors of aging. However, data on age-related changes in activities of mitochondrial electron transport chain (ETC) complexes remain controversial and molecular mechanisms responsible for ETC dysfunction are still largely unknown. In this study, we examined the effect of aging on activities of ETC complexes and oxidative damage to proteins and lipids in cardiac mitochondria from adult (6-month-old), old (15-month-old) and senescent (26-month-old) rats. ETC complexes I-IV displayed different extent of inhibition with age. The most significant decline occurred in complex IV activity, whereas complex II activity was unchanged in old rats and was only slightly reduced in senescent rats. Compared to adult, old and senescent rat hearts had significantly higher levels of malondialdehyde, 4-hydroxynonenal (HNE) and dityrosine, while thiol group content was reduced. Despite marked increase in HNE content with age (25 and 76 % for 15-and 26-month-old rats, respectively) Western blot analysis revealed only few HNE-protein adducts. The present study suggests that non-uniform decline in activities of ETC complexes is due, at least in part, to mitochondrial oxidative damage; however, lipid peroxidation products appear to have a limited impact on enzyme functions., Z. Tatarková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The aim of present study was to investigate functional and physical alterations in membranes of heart mitochondria that are associated with remodeling of these organelles in acute phase of streptozotocin-induced diabetes and to elucidate the role of these changes in adaptation of the heart to acute streptozotocin-induced diabetes (evaluated 8 days after single dose streptozotocin application to male Wistar rats). Action of free radicals on the respiratory chain of diabetic-heart mitochondria was manifested by 17 % increase (p<0.05) in oxidized form of the coenzyme Q10 and resulted in a decrease of states S3 and S4 respiration, the respiratory control index, rate of phosphorylation (all p<0.01) and the mitochondrial transmembrane potential (p<0.05), but the ADP/O ratio decreased only moderately (p>0.05). On the contrary, membrane fluidity and the total mitochondrial Mg2+-ATPase activity increased (both p<0.05). In diabetic heart mitochondria, linear regression analysis revealed a reciprocal relationship between the increase in membrane fluidity and decrease in trans-membrane potential (p<0.05, r = 0.67). Changes in membrane fluidity, transmembrane potential, Mg2+-ATPase activity and the almost preserved ADP/O ratio appear as the manifestation of endogenous protective mechanisms participating in the functional remodeling of mitochondria which contributes to adaptation of the heart to diabetes., M. Ferko, D. Habodászová, I. Waczulíková, J. Mujkošová, J. Kucharská, L. Šikurová, B. Ziegelhöffer, J. Styk, A. Ziegelhöffer., and Obsahuje bibliografii a bibliografické odkazy
Our previous preliminary results pointed to possible seasonal variations in Mg2+-ATPase activity of rat heart mitochondria (MIT). It is not too surprising since seasonal differences were already reported in myocardial function, metabolism and ultrastructure of the intact as well as hemodynamically overloaded rabbit hearts and also in other tissues. The present study is aimed to elucidate whether seasonal differences observed in rat heart MIT Mg2+-ATPase activity will be accompanied with changes in membrane fluidity and in the content of conjugated dienes (CD) in the lipid bilayers of MIT membranes as well as whether the above seasonal differences will also be present in the diabetic heart. Our results revealed that values of Mg2+-ATPase activity in the winter/spring-period (W/S-P) exceeded significantly (p<0.05-0.001) those in the summer/autumn-period (S/A-P). Similar trend was also observed in hearts of animals with acute (8 days) streptozotocin diabetes. With the exception of values of CD in the S/A-P, all values of Mg2+-ATPase activities, membrane fluidity and CD concentrations in diabetic hearts exceeded those observed in the healthy hearts. Our results indicate that seasonal differences may play a decisive role in the evaluation of properties and function of rat heart MIT., J. Mujkošová, M. Ferko, P. Humeník, I. Waczulíková, A. Ziegelhöffer., and Obsahuje bibliografii a bibliografické odkazy