Developmental changes of the sensitivity of cardiac and liver mitochondrial permeability transition pore to calcium load and oxidative stress [Internet]

Centre for Cardiovascular Research, Prague, Czech Republic.
Physiological research / Academia Scientiarum Bohemoslovaca (Impact Factor: 1.29). 07/2012; 61 Suppl 1:S165-72.
Source: PubMed


Opening of the mitochondrial membrane permeability transition pore (MPTP) is an important factor in the activation of apoptotic and necrotic processes in mammalian cells. In a previous paper we have shown that cardiac mitochondria from neonatal rats are more resistant to calcium load than mitochondria from adult animals. In this study we have analyzed the ontogenetic development of this parameter both in heart and in liver mitochondria. We found that the high resistance of heart mitochondria decreases from day 14 to adulthood. On the other hand, we did not observe a similar age-dependent sensitivity in liver mitochondria, particularly in the neonatal period. Some significant but relatively smaller increase could be observed only after day 30. When compared with liver mitochondria cardiac mitochondria were more resistant also to the peroxide activating effect on calcium-induced mitochondrial swelling. These data thus indicate that the MPTP of heart mitochondria is better protected against damaging effects of the calcium load and oxidative stress. We can only speculate that the lower sensitivity to calcium-induced swelling may be related to the higher ischemic tolerance of the neonatal heart.

Download full-text


Available from: Zuzana Cervinkova, Jan 20, 2016
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ninety per cent hepatectomy in rodents is a model for acute liver failure. It has been reported that platelets have a strong effect enhancing liver regeneration, because of the production of several growth factors such as serotonin. The aim of this study was to investigate the role of microencapsulated platelets on 90% hepatectomy in rats. Platelets (PLT) were microencapsulated in sodium alginate and implanted in the peritoneum of rats after 90% partial hepatectomy (PH). Control group received empty capsules (EC). Animals were euthanized at 6, 12, 24, 48 and 72 h post PH (n = 9-12/group/time) to evaluate liver regeneration rate, mitotic index, liver content, serum and tissue levels of Interleukin 6 (IL-6) and serotonin and its receptor 5-hydroxytryptamine type 2B (5Ht2b). Survival rate in 10 days was evaluated in a different set of animals (n = 20/group). Platelets group showed the highest survival rate despite the lowest liver regeneration rate at any time point. Mitotic and BrdU index showed no difference between groups. However, the number of hepatocytes was higher and the internuclear distance was shorter for PLT group. Liver dry weight was similar in both groups indicating that water was the main responsible factor for the weight difference. Gene expression of IL-6 in the liver was significantly higher in EC group 6 h after PH, whereas 5Ht2b was up-regulated at 72 h in PLT group. Platelets enhance survival of animals with 90% PH, probably by an early protective effect on hepatocytes and the increase in growth factor receptors.
    No preview · Article · Sep 2013 · Liver international: official journal of the International Association for the Study of the Liver
  • [Show abstract] [Hide abstract]
    ABSTRACT: Propofol is a commonly used intravenous anesthetic that has been demonstrated to be neuroprotective against cerebral ischemia-reperfusion (I/R) injury. It remains unclear whether this protective effect has any relationship with the prevention of neuronal mitochondrial deoxyribonucleic acid (mtDNA) deletion. In this study, 81 Wistar rats were randomly divided into three groups (n=27 each): sham (S group), ischemia/reperfusion (I/R group), or propofol (P group). Cerebral ischemia was induced by clamping the bilateral common carotid arteries for 10 min. A polymerase chain reaction (PCR) was conducted to determine mtDNA deletion. The mitochondrial membrane potential (MMP) changes were detected via microplate reader. The neuronal ultrastructure was visualized via electron microscope. MMP significantly decreased after I/R (p<0.05 compared with the S group). Severe damage to the ultrastructure of neuronal mitochondria was observed in cerebral I/R injury. When propofol (1.0 mg/kg/min) was administered intravenously for 1 h prior to the induction of I/R, the neuronal structure and MMP were well preserved, and mtDNA deletion was reduced after ischemia/reperfusion injury compared with the I/R group (p<0.05). These data suggested that propofol prevented mtDNA deletion and preserved a normal structure and MMP, which are important for normal mitochondrial function and increase neuronal resistance to I/R injury.
    No preview · Article · Nov 2014 · Brain Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effects of lanthanum on heat production of mitochondria isolated from Wistar rat liver were investigated with microcalorimetry; simultaneously, the effects on mitochondrial swelling and membrane potential (Δψ) were determined by spectroscopic methods. La(3+) showed only inhibitory action on mitochondrial energy turnover with IC50 being 55.8 μmol L(-1). In the spectroscopic experiments, La(3+), like Ca(2+), induced rat liver mitochondrial swelling and decreased membrane potential (Δψ), which was inhibited by the specific permeability transition inhibitor, cyclosporine A (CsA). The induction ability of La(3+) was stronger than that of Ca(2+). These results demonstrated that La(3+) had some biotoxicity effect on mitochondria; the effects of La(3+) and Ca(2+) on rat liver mitochondrial membrane permeability transition (MPT) are different, and La represents toxic action rather than Ca analogy.
    No preview · Article · Feb 2015 · Biological Trace Element Research
Show more