Quantitative evaluation of the effects of mitochondrial permeability transition pore modifiers on accumulation of calcium phosphate: comparison of rat liver and brain mitochondria

Decades of active research have shown that mitochondrial dysfunction, the associated oxidative stress, impaired anti-stress defense mechanisms, and the activation of the proapoptotic signaling pathways underlie pathological changes in organs and tissues. Pathologies caused by alcohol primarily affect the liver. Alcohol abuse is the cause of many liver diseases, such as steatosis, alcoholic steatohepatitis, fibrosis, cirrhosis, and, potentially, hepatocellular cancer. In this study, the effect of chronic alcohol exposure on rat liver mitochondria was investigated. We observed an ethanol-induced increase in sensitivity to calcium, changes in the level of protein kinase Akt and GSK-3β phosphorylation, an induction of the mitochondrial permeability transition pore (mPTP), and strong alterations in the expression of mPTP regulators. Moreover, we also showed an enhanced effect of PK11195 and PPIX, on the parameters of the mPTP opening in rat liver mitochondria (RLM) isolated from ethanol-treated rats compared to the RLM from control rats. We suggest that the results of this study could help elucidate the mechanisms of chronic ethanol action on the mitochondria and contribute to the development of new therapeutic strategies for treating the effects of ethanol-related diseases.

Download Full-text

Fractions of Adenopus breviflorus Extract Modulate Calcium-induced Mitochondrial Permeability Transition Pore Opening in Rat Liver

Annals of Science and Technology ◽

10.2478/ast-2018-0011 ◽

2018 ◽

Vol 3 (1) ◽

pp. 21-27

Author(s):

Tolulope A. Oyedeji ◽

Chibuzor I. Akobi ◽

Daniel O. Onireti ◽

Olufunso O. Olorunsogo

Keyword(s):

Rat Liver ◽

Mitochondrial Permeability Transition Pore ◽

Mitochondrial Permeability Transition ◽

Permeability Transition Pore ◽

Permeability Transition ◽

Rat Liver Mitochondria ◽

Mitochondrial Atpase ◽

Dependent Manner ◽

Mitochondrial Permeability ◽

Pore Opening

AbstractMitochondrial dysfunction (MD) and impaired apoptotic pathways cause irreversible opening of the Mitochondrial Permeability Transition (MPT) pore, resulting in several pathological conditions e.g. cancer, ageing and neurodegenerative diseases. Many bioactive compounds from plants have been identified as modulators of the MPT pore which makes them possible drugs for the management of MD associated diseases. Adenopus breviflorus (A.breviflorus) is a tropical medicinal plant used in folkore medicine as an abortifacient and in treating gonorrhoea. In this study, the effects of ethylacetate and methanol fractions of A.breviflorus were assessed on rat liver MPT pore and Mitochondrial ATPase (mATPase). The fruit of A.breviflorus was extracted with water to obtain the aqueous Extract (AEAB), which was fractionated using vacuum liquid chromatography (VLC) to obtain ethylacetate and methanol fractions of A.breviflorus (EFAB, and MFAB). The extent of MPT pore opening and mATPase by EFAB and MFAB were assayed spectrophotometrically. The results obtained showed that EFAB and MFAB have no significant inductive effect on the MPT pore in the absence of Ca2+. However, in the presence of Ca2+, EFAB inhibited calcium-induced MPT pore opening in a non-concentration dependent manner. Maximum inhibition of MPT pore opening was 57.1% at 50 μg/ml. Interestingly, MFAB potentiated calcium ion effect by opening the pore further. Specifically, MFAB opened the MPT pore by 11, 10, 17 and 9% at 50, 150, 250 and 350 μg/ml, respectively. Furthermore, EFAB and MFAB inhibited mATPase activity in rat liver mitochondria at 62.5, 187.5, 312.5 and 437.5 μg/ml by 2.6, 18.8, 37.3, 52.6% and 41.8, 6.8, 24.3, 8.4%, respectively. The ethylacetate and methanol fractions of Adenopus breviflorus possess potential phytochemicals that can modulate opening of the mitochondrial permeability transition pore and inhibit mitochondrial ATPase activity in rat liver. These fractions may find use in drug development against diseases where excessive apoptosis takes place.

Download Full-text

Amyloid β-Peptide Promotes Permeability Transition Pore in Brain Mitochondria

Bioscience Reports ◽

10.1023/a:1015536808304 ◽

2001 ◽

Vol 21 (6) ◽

pp. 789-800 ◽

Cited By ~ 76

Author(s):

Paula I. Moreira ◽

Maria S. Santos ◽

António Moreno ◽

Catarina Oliveira

Keyword(s):

Transmembrane Potential ◽

Mitochondrial Permeability Transition Pore ◽

Mitochondrial Permeability Transition ◽

Amyloid Β ◽

Permeability Transition Pore ◽

Permeability Transition ◽

Brain Mitochondria ◽

Amyloid Β Peptide ◽

Mitochondrial Permeability ◽

Pre Treatment

In this work the effect of the neurotoxic amino acid sequence, Aβ25–35, on brain mitochondrial permeability transition pore (PTP) was studied. For the purpose, the mitochondrial transmembrane potential (ΔΨm), mitochondrial respiration and the calcium fluxes were examined. It was observed that Aβ25–35, in the presence of Ca2+, decreased the ΔΨm, the capacity of brain mitochondria to accumulate calcium and led to a complete uncoupling of the respiration. However, the reverse sequence of the peptide Aβ25–35 (Aβ35–25) did not promote the PTP. The alterations promoted by Aβ35–25 and/or Ca2+ could be reversed when Ca2+ was removed by EGTA or when ADP plus oligomycin were present. The pre-treatment with CsA or ADP plus oligomycin prevented the ΔΨm drop and preserved the capacity of mitochondria to accumulate Ca2+. These results suggest that Aβ25–35 can promote the PTP induced by Ca2+.

Download Full-text