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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.

Abstract：

: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 Ca(2+)-induced mitochondrial permeability transition (MPT), as assessed by either Ca(2+)-induced mitochondrial swelling, dissipation of membrane potential or mitochondrial Ca(2+) release. The Ca(2+) 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 Ca(2+) retention capacity was preserved at this age, as compared to age-matched controls, which indicates that a reduced capacity for mitochondrial Ca(2+) 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, H(2)O(2) 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.

journal_name

Mol Genet Metab

journal_title

Molecular genetics and metabolism

authors

Figueira TR,Castilho RF,Saito A,Oliveira HC,Vercesi AE

doi

10.1016/j.ymgme.2011.08.031

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

521-8

issue

eissn

1096-7192

issn

1096-7206

pii

S1096-7192(11)00307-6

journal_volume

104

pub_type

杂志文章

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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.