ABSTRACT
Abstract The prolonged entry of large amounts of calcium into the mitochondria through the mitochondrial calcium uniporter complex (MCUC) may cause the permeability transition pore (mPTP) to open, which contributes to the pathogenesis of several diseases. Tissue-specific differences in mPTP opening due to variable expression of MCUC components may contribute to disease outcomes. We designed this study to determine differential mPTP opening in mitochondria isolated from different regions of mouse brain and kidney and to compare it with the expression of MCUC components. mPTP opening was measured using mitochondria isolated from the left/right brain hemispheres (LH/RH, respectively) and from kidney cortex/medulla, while the expression level of MCUC components was assessed from total cellular RNA. Interestingly, LH mitochondria showed less calcium-induced mPTP opening as compared to RH mitochondria at two different calcium concentrations. Conversely, mPTP opening was similar in the renal cortex and renal medulla mitochondria. However, the kidney mitochondria demonstrated bigger and faster mPTP opening as compared to the brain mitochondria. Furthermore, asymmetric mPTP opening in the LH and RH mitochondria was not associated with the expression of MCUC components. In brief, this study demonstrates thus far unreported asymmetric mPTP opening in mouse brain hemispheres that is not associated with the mRNA levels of MCUC components.
Subject(s)
Animals , Male , Female , Mice , Brain , Calcium/agonists , Cerebrum/abnormalities , Mitochondrial Permeability Transition Pore/analysis , Mice , Mitochondria , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects , Kidney CortexABSTRACT
Studies have demonstrated sympathetic cardiac denervation in the MPTP mouse model. MPTP toxicity causes sympathetic nerve damage and depletion of heart norepinephrine. Previous evaluations of impairments in heart innervation have been based on imaging, electrophysiological and biochemical methods. However, these studies lacked information that can be obtained from morphoquantitative analyses. Thus, this study aimed to apply a design-based stereological method for evaluating the morphoquantitative alterations of myocardium following treatment with the neurotoxin MPTP in the C57/BL mouse. Our results showed that MPTP reduced the number of cardiomyocytes in the left ventricle.(AU)
Estudos têm demonstrado a desnervação simpática cardíaca no modelo da administração do MPTP em camundongo. A toxicidade do MPTP causa lesão ao nervo simpático e depleção da norepinefrina. As avaliações dos danos na inervação do coração são baseadas em métodos de imagem, eletrofisiológico e bioquímico. Contudo, estes estudos carecem de informações provenientes de análises morfoquantitativas. Assim, objetivou-se aplicar métodos estereológicos para avaliar as alterações morfoquantitativas do miocárdio após o tratamento com a neurotoxina MPTP no camundongo C57/BL. Nossos resultados mostraram que o MPTP causa redução no número de cardiomiócitos no ventrículo esquerdo.(AU)