Schisandrin B stereoisomers protect against hypoxia/reoxygenation-induced apoptosis and associated changes in the Ca2+ -induced mitochondrial permeability transition and mitochondrial membrane potential in AML12 hepatocytes

2009 ◽  
Vol 23 (11) ◽  
pp. 1592-1602 ◽  
Author(s):  
Po Yee Chiu ◽  
Ka Fai Luk ◽  
Hoi Yan Leung ◽  
Ka Ming Ng ◽  
Kam Ming Ko
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Schisandrin B ◽  
Mitochondrial Permeability ◽  
Induced Apoptosis ◽  
Hypoxia Reoxygenation

scholarly journals Antimicrobial peptide CGA-N12 decreases the Candida tropicalis mitochondrial membrane potential via mitochondrial permeability transition pore

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Ruifang Li ◽  
Jiarui Zhao ◽  
Liang Huang ◽  
Yanjie Yi ◽  
Aihua Li ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Candida Tropicalis ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mitochondrial Permeability ◽  
Mptp Opening

Abstract Amino acid sequence from 65th to 76th residue of the N-terminus of Chromogranin A (CGA-N12) is an antimicrobial peptide (AMP). Our previous studies showed that CGA-N12 reduces Candida tropicalis mitochondrial membrane potential. Here, we explored the mechanism that CGA-N12 collapsed the mitochondrial membrane potential by investigations of its action on the mitochondrial permeability transition pore (mPTP) complex of C. tropicalis. The results showed that CGA-N12 induced cytochrome c (Cyt c) leakage, mitochondria swelling and led to polyethylene glycol (PEG) of molecular weight 1000 Da penetrate mitochondria. mPTP opening inhibitors bongkrekic acid (BA) could contract the mitochondrial swelling induced by CGA-N12, but cyclosporin A (CsA) could not. Therefore, we speculated that CGA-N12 could induce C. tropicolis mPTP opening by preventing the matrix-facing (m) conformation of adenine nucleotide transporter (ANT), thereby increasing the permeability of the mitochondrial membrane and resulted in the mitochondrial potential dissipation.

scholarly journals The Myxoma Poxvirus Protein, M11L, Prevents Apoptosis by Direct Interaction with the Mitochondrial Permeability Transition Pore

2002 ◽  
Vol 196 (9) ◽  
pp. 1127-1140 ◽  
Author(s):  
Helen Everett ◽  
Michele Barry ◽  
Xuejun Sun ◽  
Siow Fong Lee ◽  
Christine Frantz ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mitochondrial Permeability ◽  
Potential Loss ◽  
Mitochondrial Membrane Potential Loss

M11L, an antiapoptotic protein essential for the virulence of the myxoma poxvirus, is targeted to mitochondria and prevents the loss of mitochondrial membrane potential that accompanies cell death. In this study we show, using a cross-linking approach, that M11L physically associates with the mitochondrial peripheral benzodiazepine receptor (PBR) component of the permeability transition (PT) pore. Close association of M11L and the PBR is also indicated by fluorescence resonance energy transfer (FRET) analysis. Stable expression of M11L prevents the release of mitochondrial cytochrome c induced by staurosporine or protoporphyrin IX (PPIX), a ligand of the PBR. Transiently expressed M11L also prevents mitochondrial membrane potential loss induced by PPIX, or induced by staurosporine in combination with PK11195, another ligand of the PBR. Myxoma virus infection and the associated expression of early proteins, including M11L, protects cells from staurosporine- and Fas-mediated mitochondrial membrane potential loss and this effect is augmented by the presence of PBR. We conclude that M11L regulates the mitochondrial permeability transition pore complex, most likely by direct modulation of the PBR.

scholarly journals The role of the mitochondria in apoptosis induced by 7β-hydroxycholesterol and cholesterol-5β,6β-epoxide

2005 ◽  
Vol 94 (4) ◽  
pp. 519-525 ◽  
Author(s):  
Lisa Ryan ◽  
Yvonne C. O'Callaghan ◽  
Nora M. O'Brien
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Apoptotic Pathways ◽  
Induced Apoptosis

Oxysterols are oxygenated derivatives of cholesterol that may be formed endogenously or absorbed from the diet. Significant amounts of oxysterols have frequently been identified in foods of animal origin, in particular highly processed foods. To date, oxysterols have been shown to possess diverse biological activities; however, recent attention has focused on their potential role in the development of atherosclerosis. Oxysterols have been reported to induce apoptosis in cells of the arterial wall, a primary process in the development of atheroma. The aim of the present study was to identify the role of the mitochondria in the apoptotic pathways induced by the oxysterols 7β-hydroxycholesterol (7β-OH) and cholesterol-5β,6β-epoxide (β-epoxide) in U937 cells. To this end, we investigated the effects of these oxysterols on mitochondrial membrane potential, caspase-8 activity, the mitochondrial permeability transition pore and cytochrome c release. 7β-OH-induced apoptosis was associated with a loss in mitochondrial membrane potential after 2 h, accompanied by cytochrome c release from the mitochondria into the cytosol after 16 h. Pre-treatment with a range of inhibitors of the mitochondrial permeability transition pore protected against 7β-OH-induced cell death. In contrast, β-epoxide induced a slight increase in caspase-8 activity but had no effect on mitochondrial membrane potential or cytochrome c release. The present results confirm that 7β-OH-induced apoptosis occurs via the mitochondrial pathway and highlights differences in the apoptotic pathways induced by 7β-OH and β-epoxide in U937 cells.

Two mechanisms by which ATP depletion potentiates induction of the mitochondrial permeability transition

1997 ◽  
Vol 273 (2) ◽  
pp. C479-C488 ◽  
Author(s):  
G. Simbula ◽  
P. A. Glascott ◽  
S. Akita ◽  
J. B. Hoek ◽  
J. L. Farber
Keyword(s):  
Cell Death ◽  
Membrane Potential ◽  
Liver Cell ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Atp Depletion ◽  
Mitochondrial Permeability ◽  
A 23187 ◽  
Liver Cell Death

The present and a previous study [J. W. Snyder, J. G. Pastorino, A. M. Attie, and J. L. Farber, Am. J. Physiol. 264 (Cell Physiol. 33): C709-C714, 1993] define two mechanisms whereby ATP depletion promotes liver cell death. ATP depletion and cell death are linked by the mitochondrial permeability transition (MPT). Mitochondrial deenergization promotes the MPT, and ATP maintains a membrane potential by reversal of ATP synthase. With an increased influx of Ca2+ induced by the ionophore A-23187, oligomycin depleted the cells of ATP without loss of the mitochondrial membrane potential and further elevated the intracellular Ca2+ concentration. Cyclosporin A (CyA) prevented the accompanying cell killing. Fructose also preserved the viability of the cells. With the increased cytosolic Ca2+ imposed by A-23187, viability is maintained by ATP-dependent processes. Upon depletion of ATP, Ca2+ homeostasis cannot be maintained, and the MPT is induced. Rotenone also depleted the cells of ATP, and A-23187 accelerated the loss of the mitochondrial membrane potential occurring with rotenone alone. CyA and fructose prevented the cell killing with rotenone and A-23187. Oligomycin did not prevent this action of fructose. We conclude that ATP is needed to maintain Ca2+ homeostasis to prevent the MPT and the resultant liver cell death. ATP is also needed to maintain mitochondrial energization when electron transport is inhibited.

scholarly journals Erinacine Facilitates the Opening of the Mitochondrial Permeability Transition Pore Through the Inhibition of the PI3K/ Akt/GSK-3β Signaling Pathway in Human Hepatocellular Carcinoma

2018 ◽  
Vol 50 (3) ◽  
pp. 851-867 ◽  
Author(s):  
Li-Jie Zhou ◽  
Yan-Bo Mo ◽  
Xuan Bu ◽  
Jian-Jun Wang ◽  
Jing Bai ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Signaling Pathway ◽  
Mitochondrial Membrane Potential ◽  
Colony Formation ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Cyt C ◽  
Gsk 3Β

Background/Aims: Erinacine, which is extracted from the medicinal mushroom Hericium erinaceus, is known to play anticancer roles in human cancers. The following study aims to investigate the role of erinacine in the opening of the mitochondrial permeability transition pore (MPTP) in hepatocellular carcinoma (HCC) through the PI3K/Akt/GSK-3β signaling pathway and highlights the applicability of erinacine in HCC treatments. Methods: HCC and paracancerous tissues were obtained from 85 HCC patients who’ve undergone surgical resection. Immunohistochemistry was adopted to detect positive expression of PI3K, Akt, and GSK-3β. Treatment of HepG-2 with LY294002 (an inhibitor of the PI3K/Akt/GSK-3β signaling pathway) and different concentration of erinacine was performed to determine the involvement of LY294002 in erinacine action. The expressions of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, Bcl-2, E-cadherin, Bax, and caspase-9 were determined by RT-qPCR and Western blot analysis. Cell viability, colony formation rate, migration, invasion, cycle, and apoptosis were detected by MTT, colony formation, wound healing assay, Transwell assay, and flow cytometry, respectively. The size and weight of xenograft tumors were observed in nude mice. Mitochondrial membrane potential in HepG-2 was determined using laser scanning confocal microscopy following JC-1 staining. Mitochondrial Ca2+ indicator Rhod-2, AM was used to detect the changes of mitochondrial Ca2+, while western blot analysis was employed to detect the presence levels of cytochrome C (cyt-C). Results: The results revealed that PI3K, Akt, and GSK-3β were up-regulated in HCC tissues. Erinacine or LY294002 led to a decrease in mitochondrial membrane potential, increase in intracellular mitochondrial Ca2+, and the release of cyt-C in mitochondria. In addition, Erinacine was found to decrease the mitochondrial membrane potential, expression of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, and Bcl-2, cell proliferation, colony formation ability, migration, invasion, and xenograft tumor size, while E-cadherin, Bax, and caspase-9 expression, and cell apoptosis were elevated in a dose-dependent manner. Erinacine also stimulated the effects of LY294002 on the HCC. Following the addition of 500 μM Erinacine and MPTP opening inhibitor CsA, we found that the mitochondrial membrane potential level increased, while mitochondrial Ca2+ and Cyt-C decreased from the mitochondria. Conclusion: The results from the study demonstrated that erinacine induced MPTP opening, facilitates the release of cyt-C, and inhibited cell proliferation, migration, and invasion, while it promotes apoptosis by inactivating the PI3K/Akt/GSK-3β signaling pathway, preventing the progression of HCC.

Sign in / Sign up

Export Citation Format

Share Document