Mitochondrial Permeability Transition Pore in Inflammatory Apoptosis of Human Conjunctival Epithelial Cells and T Cells: Effect of Cyclosporin A

Gao, Jianping; Sana, Reuben; Calder, Virginia L.; Calonge, Margarita; Lee, Wanju; Wheeler, Larry A.; Stern, Michael E.

doi:10.1167/iovs.13-11681

Cited by 72 publications

(46 citation statements)

References 44 publications

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“…Furthermore, a transient 'flickering' mode of mPTP opening has also been described in the literature playing a role in ROS-mediated signaling and adaptive cellular stress responses. 41,42 A cyclosporin A-insensitive ionomycin-induced pore opening was also found in our cell system, similar to what was described in other types of cells, 43 which could indicate alternative mitochondrial membrane permeabilization mechanisms. Ionomycin-induced mPTP opening also appeared to be dependent on differentiation state: the more undifferentiated cells (Glu-P19SCs) presented the highest resistance to pore induction.…”

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confidence: 88%

Mitochondrial metabolism directs stemness and differentiation in P19 embryonal carcinoma stem cells

et al. 2014

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The relationship between mitochondrial metabolism and cell viability and differentiation in stem cells (SCs) remains poorly understood. In the present study, we compared mitochondrial physiology and metabolism between P19SCs before/after differentiation and present a unique fingerprint of the association between mitochondrial activity, cell differentiation and stemness. In comparison with their differentiated counterparts, pluripotency of P19SCs was correlated with a strong glycolytic profile and decreased mitochondrial biogenesis and complexity: round, low-polarized and inactive mitochondria with a closed permeability transition pore. This decreased mitochondrial capacity increased their resistance against dichloroacetate. Thus, stimulation of mitochondrial function by growing P19SCs in glutamine/pyruvate-containing medium reduced their glycolytic phenotype, induced loss of pluripotent potential, compromised differentiation and became P19SCs sensitive to dichloroacetate. Because of the central role of this type of SCs in teratocarcinoma development, our findings highlight the importance of mitochondrial metabolism in stemness, proliferation, differentiation and chemoresistance. In addition, the present work suggests the regulation of mitochondrial metabolism as a tool for inducing cell differentiation in stem line therapies. Embryonal carcinoma cells, including the P19 cell line, are pluripotent cancer stem cells (CSCs) derived from pluripotent germ cell tumors called teratocarcinomas. These have been described as the malignant counterparts of embryonic stem cells (ESCs) and are considered a good model to study stem cell (SC) differentiation. The P19 cell line can be maintained as undifferentiated cells (P19SCs) or differentiated (P19dCs) to any cell type of the three germ layers. Similar to ESCs, P19 cells differentiate with retinoic acid (RA) in a dose-dependent manner and depending on growth conditions. 1 Although differentiation generally yields a mixed population of differentiated cells, P19 cells grown in monolayer and treated with 1 mM RA primarily differentiate in endoderm or mesoderm, while retaining their immortality. 2,3Although some therapeutic approaches for regenerative medicine and to targeting CSCs are based on differentiation 4 and mitochondrial-targeted therapies, 5,6 very little is known about the role of mitochondrial metabolism in SC maintenance and differentiation.7 Several mitochondrial characteristics that distinguish transformed cells from healthy cells have been described, 8 including increased mitochondrial transmembrane electric potential (Dcm), which may result from decreased mitochondrial ATP production under normoxia. Similarly, normal SCs primarily rely on glycolysis for energy supply, although the exact mechanism how this occurs in the presence of oxygen and the relationship between SC metabolism and cell fate control is not yet completely understood. 10Given the mitochondrial involvement in stemness and differentiation, 11 one can ask whether manipulation of mitochondrial physi...

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confidence: 88%

Mitochondrial metabolism directs stemness and differentiation in P19 embryonal carcinoma stem cells

et al. 2014

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“…The loss of mitochondrial membrane potential is an indication of irreversible cell injury, which induces cell apoptosis (Gao et al 2013). We found that the mitochondrial membrane potential decreased and the apoptosis rate increased in NaF-treated Sertoli cells, and there was a significant doseresponse relationship between NaF and MMP, similar results also appeared on the relationship between NaF and apoptosis rate.…”

Section: Discussionsupporting

confidence: 68%

Effect of oxidative stress on fluoride-induced apoptosis in primary cultured Sertoli cells of rats

Yang

Huang

et al. 2014

International Journal of Environmental Health Research

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This study examined the effect of oxidative stress on the apoptosis of Sertoli cells induced by sodium fluoride (NaF). Cell viability, reactive oxygen species, malondialdehyde content, superoxide dismutase activity, mitochondrial membrane potential, and apoptosis were measured after the rat Sertoli cells were exposed to various concentrations of (0, 6, 12, and 24 μg/ml) sodium fluoride in the presence and absence of 2 mM N-acetylcysteine (NAC) for 24 h. The present study showed that decrease in cell viability and excessive oxidative stress were observed in NaF-treated cells. The treatment with NAC restored the decreased cell viability and excessive oxidative stress. Moreover, fluoride exposure decreased mitochondrial membrane potential and increased apoptosis in Sertoli cells. NAC was also found to suppress a loss of mitochondrial membrane potential and the percentage of apoptosis in NaF-treated Sertoli cells. This study proved that oxidative stress probably play a major role in NaF-induced apoptosis of Sertoli cells.

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“…Studies have demonstrated that collapse of the mitochondrial membrane potential due to opening of the MPT pore typically triggers apoptosis (Qanungo et al, 2005;Gao et al, 2013;Ramkumar et al, 2013). The loss of mitochondrial membrane potential in MP3-treated cells supports the observed cytotoxic activity of the fraction in the MTT assay.…”

Section: Discussionmentioning

confidence: 52%

Apoptosis-Inducing Activity of HPLC Fraction from Voacanga globosa (Blanco) Merr. on the Human Colon Carcinoma Cell Line, HCT116

Acebedo

Amor²,

Jacinto³

2014

Asian Pacific Journal of Cancer Prevention

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likely to produce anti-cancer compounds. Using MTT assay, the study aimed to test HPLC fractions from the V globosa leaf extract for cytotoxicity against the HCT116 human colon carcinoma, A549 human lung carcinoma and the non-cancer AA8 Chinese hamster ovarian cell lines. Possible pro-apoptotic activity was also assessed using DAPI nuclear staining, TUNEL assay and the JC-1 mitochondrial membrane potential assay. Production of the ethanolic crude extractMature leaves from V globosa (Blanco) Merr. wereInstitute of Biology, University of the Philippines Diliman (a voucher specimen sample submitted was assigned the accession number: 14609). Leaves were air dried until crispy and then macerated in 95% technical grade ethanol

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Mitochondrial Permeability Transition Pore in Inflammatory Apoptosis of Human Conjunctival Epithelial Cells and T Cells: Effect of Cyclosporin A

Cited by 72 publications

References 44 publications

Mitochondrial metabolism directs stemness and differentiation in P19 embryonal carcinoma stem cells

Mitochondrial metabolism directs stemness and differentiation in P19 embryonal carcinoma stem cells

Effect of oxidative stress on fluoride-induced apoptosis in primary cultured Sertoli cells of rats

Apoptosis-Inducing Activity of HPLC Fraction from Voacanga globosa (Blanco) Merr. on the Human Colon Carcinoma Cell Line, HCT116

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