- MeSH
- lidé MeSH
- trombocytopatie * genetika metabolismus MeSH
- trombocyty MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
OBJECTIVES: The bipolar affective disorder (BAD) pathophysiology is multifactorial and has not been fully clarified. METHOD: We measured selected mitochondrial parameters in peripheral blood components. The analyses were performed for patients suffering from a manic episode during remission and were compared to those performed for healthy controls. BAD was clinically evaluated using well-established diagnostic scales and questionnaires. Mitochondrial respiration was examined in intact and permeabilized blood platelets using high-resolution respirometry. The citrate synthase (CS) and electron transport system (ETS) complex (complex I, II, and IV) activities were examined in platelets. RESULTS: The CS, complex II and complex IV activities were decreased in the BAD patients, complex I activity was increased, and the ratio of complex I to CS was significantly increased. In the intact platelets, respiration after complex I inhibition and residual oxygen consumption were decreased in the BAD patients compared to the healthy controls. In the permeabilized platelets, a decreased ETS capacity was found in the BAD patients. No significant differences were found between BAD patients in mania and remission. CONCLUSION: Increased complex I activity can be a compensatory mechanism for decreased CS and complex II and IV activities. We conclude that complex I and its abnormal activity contribute to defects in cellular energy metabolism during a manic episode and that the deficiency in the complex's functioning, but not the availability of oxidative phosphorylation substrates, seems to be responsible for the decreased ETS capacity in BAD patients. The observed parameters can be further evaluated as 'trait' markers of BAD.
- MeSH
- bipolární porucha komplikace farmakoterapie metabolismus MeSH
- citrátsynthasa metabolismus MeSH
- dospělí MeSH
- elektronový transportní řetězec metabolismus MeSH
- lidé MeSH
- mitochondrie metabolismus MeSH
- trombocytopatie komplikace metabolismus MeSH
- trombocyty metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
STIM1 and Orai1 are key components of the Ca2+-release activated Ca2+ (CRAC) current. Orai1, which represents the subunit forming the CRAC channel complex, is activated by the ER resident Ca2+ sensor STIM1. The genetically inherited Stormorken syndrome disease has been associated with the STIM1 single point R304W mutant. The resulting constitutive activation of Orai1 mainly involves the CRAC-activating domain CAD/SOAR of STIM1, the exposure of which is regulated by the molecular interplay between three cytosolic STIM1 coiled-coil (CC) domains. Here we present a dual mechanism by which STIM1 R304W attains the pathophysiological, constitutive activity eliciting the Stormorken syndrome. The R304W mutation induces a helical elongation within the CC1 domain, which together with an increased CC1 homomerization, destabilize the resting state of STIM1. This culminates, even in the absence of store depletion, in structural extension and CAD/SOAR exposure of STIM1 R304W leading to constitutive CRAC channel activation and Stormorken disease.
- MeSH
- abnormální erytrocyty metabolismus patologie MeSH
- bakteriální proteiny genetika metabolismus MeSH
- bodová mutace * MeSH
- dyslexie genetika metabolismus patologie MeSH
- exprese genu MeSH
- HEK293 buňky MeSH
- ichtyóza genetika metabolismus patologie MeSH
- interakční proteinové domény a motivy MeSH
- iontový transport MeSH
- konformace proteinů, alfa-helix MeSH
- lidé MeSH
- luminescentní proteiny genetika metabolismus MeSH
- metoda terčíkového zámku MeSH
- migréna genetika metabolismus patologie MeSH
- mióza genetika metabolismus patologie MeSH
- molekulární modely MeSH
- multimerizace proteinu MeSH
- nádorové proteiny chemie genetika metabolismus MeSH
- protein ORAI1 chemie genetika metabolismus MeSH
- protein STIM1 chemie genetika metabolismus MeSH
- regulace genové exprese MeSH
- rekombinantní proteiny chemie genetika metabolismus MeSH
- reportérové geny MeSH
- sekvence aminokyselin MeSH
- slezina abnormality metabolismus patologie MeSH
- substituce aminokyselin MeSH
- svalová únava genetika MeSH
- trombocytopatie genetika metabolismus patologie MeSH
- vápník chemie metabolismus MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- zelené fluorescenční proteiny genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
