The higher susceptibility of congenital analbuminemic rats to Ca²⁺-induced mitochondrial permeability transition is associated with the increased expression of cyclophilin D and nitrosothiol depletion
2011
Figueira, Tiago R. | Castilho, Roger F. | Saito, Ângela | Oliveira, Helena C.F. | Vercesi, Anibal E.
Congenital analbuminemia is a rare autosomal recessive disorder characterized by a trace level of albumin in blood plasma and mild clinical symptoms. Analbuminemic patients generally present associated abnormalities, among which dyslipidemia is a hallmark. In this study, we show that mitochondria isolated from different tissues (liver, heart and brain) from 3-month-old analbuminemic rats (NAR) present a higher susceptibility to Ca²⁺-induced mitochondrial permeability transition (MPT), as assessed by either Ca²⁺-induced mitochondrial swelling, dissipation of membrane potential or mitochondrial Ca²⁺ release. The Ca²⁺ retention capacity of the liver mitochondria isolated from 3-month-old NAR was about 50% that of the control. Interestingly, the assessment of this variable in 21-day-old NAR indicated that the mitochondrial Ca²⁺ retention capacity was preserved at this age, as compared to age-matched controls, which indicates that a reduced capacity for mitochondrial Ca²⁺ retention is not a constitutive feature. The search for putative mediators of MPT sensitization in NAR revealed a 20% decrease in mitochondrial nitrosothiol content and a 30% increase in cyclophilin D expression. However, the evaluation of other variables related to mitochondrial redox status showed similar results between the controls and NAR, i.e., namely the contents of reduced mitochondrial membrane protein thiol groups and total glutathione, H₂O₂ release rate, and NAD(P)H reduced state. We conclude that the higher expression of cyclophilin D, a major component of the MPT pore, and decreased nitrosothiol content in NAR mitochondria may underlie MPT sensitization in these animals.
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