Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are effective drugs in the treatment of hypercholesterolemia, however, their undesirable actions are not fully known. We investigated the effects of atorvastatin on the oxidative phosphorylation and membrane fluidity in liver mitochondria, and also on the coenzyme Q (CoQ) content in the mitochondria, liver tissue, and plasma of rats on a standard (C) and hypercholesterolemic (HCh) diet. Atorvastatin was administered at either low (10 mg⋅kg-1) or high dose (80 mg⋅kg-1) for four weeks. The high dose of the drug decreased the concentrations of total cholesterol and triacylglycerols in the plasma and liver of rats on a HCh diet. Administration of atorvastatin was associated with decreased oxygen uptake (state 3), and oxidative phosphorylation rate in the mitochondria of both C and HCh rats. Further, the drug influenced mitochondrial membrane fluidity and dose-dependently reduced concentrations of oxidized and reduced forms of CoQ in the mitochondria. Our findings point to an association between in vivo administration of atorvastatin and impaired bioenergetics in the liver mitochondria of rats, regardless of diet, in conjunction with simultaneous depletion of oxidized and reduced CoQ forms from the mitochondria. This fact may play a significant role in the development of statin-induced hepatopathy.

• MeSH
• cholesterol farmakologie   MeSH
• dieta MeSH
• hypercholesterolemie metabolismus   MeSH
• jaterní mitochondrie metabolismus   MeSH
• játra metabolismus   MeSH
• krysa rodu rattus MeSH
• kyseliny heptylové aplikace a dávkování   terapeutické užití   MeSH
• mikroživiny farmakologie   metabolismus   MeSH
• pyrroly aplikace a dávkování   terapeutické užití   MeSH
• statiny aplikace a dávkování   terapeutické užití   MeSH
• ubichinon farmakologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• financování organizované MeSH
• Publikační typ
• abstrakty MeSH

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 Q(10) 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.

• MeSH
• Ca(2+)-Mg(2+)-ATPasa metabolismus   MeSH
• experimentální diabetes mellitus metabolismus   patofyziologie   MeSH
• fluidita membrány MeSH
• fyziologická adaptace MeSH
• krysa rodu rattus MeSH
• membránový potenciál mitochondrií MeSH
• mitochondriální membrány metabolismus   MeSH
• myokard enzymologie   metabolismus   MeSH
• oxidativní fosforylace MeSH
• potkani Wistar MeSH
• srdeční mitochondrie enzymologie   metabolismus   MeSH
• transport elektronů MeSH
• ubichinon analogy a deriváty   metabolismus   MeSH
• volné radikály metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• erytrocytární membrána enzymologie   fyziologie   účinky záření   MeSH
• erytrocyty fyziologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• fotochemoterapie metody   využití   MeSH
• laserová terapie s nízkou intenzitou světla metody   využití   MeSH
• lidé MeSH
• pyrimidinony farmakokinetika   krev   MeSH
• sodíko-draslíková ATPasa fyziologie   krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

• MeSH
• buněčná membrána fyziologie   MeSH
• fluorescenční barviva MeSH
• fosfolipidy MeSH
• liposomy metabolismus   MeSH
• sérový albumin hovězí fyziologie   MeSH
• spektrální analýza MeSH

Chronic kidney disease (CKD) is associated with increased concentration of intracellular calcium, which is pathological and may lead to irreversible damage of cell functions and structures. The aim of our study was to investigate the impact of 6 months vitamin D(3) supplementation (14 000 IU/week) on free cytosolic calcium concentration ([Ca(2+)](i)) and on the plasma membrane calcium ATPase (PMCA) activity of patients with CKD stage 2-3. PMCA activity of patients was also compared to that of healthy volunteers. Vitamin D(3) supplementation of CKD patients resulted in the decrease of [Ca(2+)](i) (119.79+/-5.87 nmol/l vs. 105.36+/-3.59 nmol/l, n=14, P<0.001), whereas PMCA activity of CKD patients (38.75+/-22.89 nmol P(i)/mg/h) remained unchanged after vitamin D(3) supplementation (40.96+/-17.74 nmol P(i)/mg/h, n=14). PMCA activity of early stage CKD patients before supplementation of vitamin D(3), was reduced by 34 % (42.01+/-20.64 nmol P(i)/mg/h) in comparison to healthy volunteers (63.68+/-20.32 nmol P(i)/mg/h, n=28, P<0.001). These results indicate that vitamin D(3) supplementation had a lowering effect on [Ca(2+)](i) and negligible effect on PMCA activity in CKD patients.

• MeSH
• ATPasy přenášející vápník přes plazmatickou membránu metabolismus   MeSH
• cholekalciferol terapeutické užití   MeSH
• chronická renální insuficience komplikace   enzymologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nedostatek vitaminu D enzymologie   etiologie   prevence a kontrola   MeSH
• potravní doplňky MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• vápník metabolismus   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH

Membrane fluidity is a widely recognized biophysical variable that provides information about structural organization of the subcellular membranes exhibiting physical characteristics of liquid crystals. The term “fluidity” reflects in this case the tightness in packing of acyl parts of the membrane phospholipid molecules, a feature that may influence considerably the molecular mobility and via that also the sensitivity and reactivity of membranebound transporters, receptors and enzyme systems. Data presented in this review are aimed to demonstrate the substantial role of changes in membrane fluidity occurring in the processes associated with endogenous protection observed in cardiac sarcolemma and mitochondria in diverse pathologies, particularly in diabetes and hypertension.

• MeSH
• buněčná membrána metabolismus   MeSH
• fluidita membrány fyziologie   MeSH
• fosfolipidy metabolismus   MeSH
• krysa rodu rattus MeSH
• membránové lipidy metabolismus   MeSH
• myokard metabolismus   MeSH
• sarkolema metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

• Publikační typ
• abstrakt z konference MeSH

• MeSH
• erytrocyty MeSH
• neuraminidasa MeSH
• permeabilita buněčné membrány MeSH
• virové receptory MeSH

In this study, we report for the first time concurrent measurements of membrane potential and dynamics and respiratory chain activities in rat heart mitochondria, as well as calcium transients in the hearts of rats in an early phase of streptozotocin diabetes, not yet accompanied with diabetes-induced complications. Quantitative relationships among these variables were assessed. The mitochondria from diabetic rats exhibited decreased fluorescence anisotropy values of diphenylhexatriene. This indicates that hydrophobic core of the membranes was more fluid compared with controls (p<0.05). We discuss the changes in fluidity as having been associated with augmented energy transduction through the diabetic membranes. Reduced ratio of JC-1 fluorescence (aggregates to monomers) in the mitochondria from diabetic hearts reflected descendent transmembrane potential. A significant negative association between membrane fluidity and potential in the diabetic group was found (p<0.05; r=0.67). Further, we observed an increase in calcium transient amplitude (CTA) in the diabetic cardiomyocytes (p=0.048). We conclude that some of the calcium-induced regulatory events that dictate fuel selection and capacity for ATP production in diabetic heart occur at the membrane level. Our findings offer new insight into acute diabetes-induced changes in cardiac mitochondria.

• MeSH
• experimentální diabetes mellitus metabolismus   patofyziologie   MeSH
• financování organizované MeSH
• fluidita membrány MeSH
• kardiomyocyty metabolismus   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• membránový potenciál mitochondrií MeSH
• mitochondriální membrány fyziologie   MeSH
• myokard metabolismus   MeSH
• oxidativní fosforylace MeSH
• potkani Wistar MeSH
• spotřeba kyslíku MeSH
• srdce patofyziologie   MeSH
• srdeční komory cytologie   MeSH
• srdeční mitochondrie fyziologie   MeSH
• vápník fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH