Galectin-3 but not galectin-1 induces mast cell death by oxidative stress and mitochondrial permeability transition

The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to tert-butyl hydroperoxide (t-BOOH)-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca2+ chelator BAPTA, the L-type Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.

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Complement 1q-binding protein inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death

Biochemical Journal ◽

10.1042/bj20101431 ◽

2010 ◽

Vol 433 (1) ◽

pp. 119-125 ◽

Cited By ~ 29

Author(s):

Allison M. McGee ◽

Christopher P. Baines

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Mitochondrial Permeability Transition Pore ◽

Mitochondrial Permeability Transition ◽

Binding Protein ◽

Critical Role ◽

Permeability Transition Pore ◽

Permeability Transition ◽

Critical Event ◽

Mitochondrial Permeability

Opening of the MPT (mitochondrial permeability transition) pore is a critical event in mitochondrial-mediated cell death. However, with the exception of CypD (cyclophilin D), the exact molecular composition of the MPT pore remains uncertain. C1qbp (complement 1q-binding protein) has recently been hypothesized to be an essential component of the MPT pore complex. To investigate whether C1qbp indeed plays a critical role in MPT and cell death, we conducted both gain-of-function and loss-of-function experiments in MEFs (mouse embryonic fibroblasts). We first confirmed that C1qbp is a soluble protein that localizes to the mitochondrial matrix in mouse cells and tissues. Similarly, overexpression of C1qbp in MEFs using an adenovirus resulted in its exclusive localization to mitochondria. To our surprise, increased C1qbp protein levels actually suppressed H2O2-induced MPT and cell death. Antithetically, knockdown of endogenous C1qbp with siRNA (small interfering RNA) sensitized the MEFs to H2O2-induced MPT and cell death. Moreover, we found that C1qbp could directly bind to CypD. Therefore C1qbp appears to act as an endogenous inhibitor of the MPT pore, most likely through binding to CypD, and thus protects cells against oxidative stress.

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Faculty Opinions recommendation of Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1025130.301711 ◽

2005 ◽

Author(s):

Atan Gross

Keyword(s):

Cell Death ◽

Mitochondrial Permeability Transition ◽

Critical Role ◽

Permeability Transition ◽

Cyclophilin D ◽

Mitochondrial Permeability

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Faculty Opinions recommendation of Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1025130.297852 ◽

2005 ◽

Author(s):

Robert Sapolsky

Keyword(s):

Cell Death ◽

Mitochondrial Permeability Transition ◽

Critical Role ◽

Permeability Transition ◽

Cyclophilin D ◽

Mitochondrial Permeability

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Metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female Wistar rats

Bulletin of the National Research Centre ◽

10.1186/s42269-021-00562-6 ◽

2021 ◽

Vol 45 (1) ◽

Author(s):

Adeola Oluwakemi Olowofolahan ◽

Obinna Matthew Paulinus ◽

Heritage Mojisola Dare ◽

Olufunso Olabode Olorunsogo

Keyword(s):

Cell Death ◽

Cytochrome C ◽

Mitochondrial Permeability Transition ◽

Permeability Transition ◽

Estradiol Benzoate ◽

Histological Evaluation ◽

Mitochondrial Atpase ◽

Rat Uterus ◽

Mitochondrial Permeability ◽

Pore Opening

Abstract Background Some antitumor or anticancer agents have been shown to execute cell death by induction of mitochondrial permeability transition (mPT) pore opening in order to elicit their chemotherapeutic effect. Therefore, this study investigated the effect of metformin on cell death via rat uterus mPT pore and estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female rat. Mitochondria were isolated using differential centrifugation. The mPT pore opening, cytochrome c release and mitochondrial ATPase activity were determined spectrophotometrically. Caspases 9 and 3 activities, MDA and estradiol levels and SOD, GSH activities, were determined using ELISA technique. Histological and histochemical assessments of the uterine section were carried out using standard methods. Results Metformin at concentrations 10–90 μg/mL, showed no significant effect on mPT pore opening, mATPase activity and release of cytochrome c. However, oral administration of metformin caused mPT pore opening, enhancement of mATPase activity and activation of caspases 9 and 3 significantly at 300 and 400 mg/kg. Metformin protected against estradiol benzoate (EB)-induced uterine defect and other associated pathophysiological disorder. It also improved the antioxidant defense system. The histological evaluation revealed the protective effect of metformin on the cellular architecture of the uterus while the histochemical examination showed severe hyperplasia in the uterine section of EB-treated rats, remarkably reversed by metformin co-treatment. Conclusion This study suggests that metformin at high doses induces apoptosis via rat uterus mPT pore opening and protects against EB-induced uterine defect (hyperplasia) and associated pathophysiological disorder.

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