Cyclosporine A prevents apoptosis-related mitochondrial dysfunction after neonatal cardioplegic arrest

Oka, Norihiko; Wang, Lixing; Mi, Wenyu; Zhu, Wei; Honjo, Osami; Caldarone, Christopher A.

doi:10.1016/j.jtcvs.2007.05.009

Cited by 47 publications

(43 citation statements)

References 35 publications

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“…3a). Treatment with mitochondrial permeability transition pore inhibitor, cyclosporin A [21], attenuated the gefitinib-induced collapse in mitochondrial membrane potential (Fig. 3a).…”

Section: Bax Involvement In Gefitinib-induced Apoptosismentioning

confidence: 87%

Gefitinib induces apoptosis in human glioma cells by targeting Bad phosphorylation

Chang

Shen

et al. 2011

J Neurooncol

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Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is under clinical testing and use in cancer patients, including glioma. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma remain largely uncharacterized. Gefitinib inhibits cell growth and induces apoptosis in human glioma cells. Gefitinib also induces death of H4 cells with characteristics of the intrinsic apoptotic pathway, including Bax mitochondrial translocation, mitochondrial outer membrane permeabilization, cytochrome c cytosolic release, and caspase-9/caspase-3 activation. The importance of Bax in mediating gefitinib-induced apoptosis was confirmed by the attenuation of apoptosis by Bax siRNA and Bax channel blocker. Gefitinib caused Bad dephosphorylation, particularly in serine-112, and increased its binding preference to Bcl-2 and Bcl-xL. The dephosphorylation of Bad in gefitinib-treated cells was accompanied by reduced intracellular cyclic AMP content and protein kinase A (PKA) activity. Adenylyl cyclase activator forskolin attenuated, but PKA inhibitor H89 augmented, gefitinib-induced Bad dephosphorylation, Bax mitochondrial translocation, caspase-9/caspase-3 activation, and viability loss. Intriguingly, a nonselective protein phosphatase inhibitor okadaic acid alleviated gefitinib-induced alterations, except Bad dephosphorylation. In parallel with the higher basal PKA activity, response of U87 cells to gefitinib treatment was delayed and relatively resistant compared with that of H4 and T98G cells. Inactivation of PKA sensitized H4, T98G, and U87 cells to gefitinib cytotoxicity, Bad dephosphorylation in serine-112, and caspase-9/caspase-3 activation. Our findings suggest the involvement of the Bad/Bax signaling pathway in gefitinib-induced glioma apoptosis. Furthermore, the inactivation of PKA was shown to play a role in triggering the proapoptotic function of Bad.

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“…3a). Treatment with mitochondrial permeability transition pore inhibitor, cyclosporin A [21], attenuated the gefitinib-induced collapse in mitochondrial membrane potential (Fig. 3a).…”

Section: Bax Involvement In Gefitinib-induced Apoptosismentioning

confidence: 87%

Gefitinib induces apoptosis in human glioma cells by targeting Bad phosphorylation

Chang

Shen

et al. 2011

J Neurooncol

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“…Experimental results from research on cardioplegia suggest that classical cold crystalloid cardioplegia is not the best solution and does not provide 100% protection (Reichard and Opie 1989;Soncul et al 1992a;Soncul et al 1992b;Kerendi et al 2006;Hsieh et al 2007;Choi et al 2007;Sodha et al 2008;Oka et al 2008;Khabbaz et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Comparison of various methods of ischaemic cardioprotection on vitality of rat heart grafts

et al. 2017

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The aim of the study was to compare 4 modes of ischaemic cardioprotection using continuous prograde autologous blood perfusion of the coronary artery in two hypothermic modes (group A, B) or conventional protection by cooled Hartmann solution (group C) or cooled saline (group D) without perfusion of the graft. Male Wistar rats (n = 24) were divided into four groups (A-D). In groups A (22-25 °C) and B (4-8 °C), blood perfusion rate was 10 ml/h and the graft was placed in a water bath. Groups C, D were initially rinsed with cold (4-8 °C) Hartmann solution (C) and cold saline solution (D), next the graft was placed in a water bath of cold (4-8 °C) Hartmann solution (C) or saline solution (D). The observed time was 30 min after the implemented perfusion (A, B) or initial rinsing (C, D). At 30 min, hearts of all the groups were perfused for 10 min with prograde-autologous arterialized blood at room temperature. At perfusion minute 10, blood was collected for biochemical analysis (sample 1). Sample 2 involved blood from a portable syringe infusion pumps (in parallel with sample 1). Pairwise test differences between samples 1 and 2 were significant in all the groups as regards creatine kinase and lactate dehydrogenase values, sampling 1 values being always higher, while cardiac troponin I concentrations were nonsignificant in the same comparison. The heart rate during the final perfusion was identical in all the groups. Our study has demonstrated that all observed cardioprotection modes are useful for experimental heart grafting. Blood hypothermic cardioprotection, crystaloid hypothermic cardioprotection

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“…Nevertheless, it can be assumed that ischemia-induced apoptosis similarly occurs in neonatal and adult hearts. It has been shown that opening of the mitochondrial permeability transition pore takes place in neonatal piglets [16,17] and neonatal rats [18] because cyclosporine A, an inhibitor of mitochondrial permeability transition pore opening, prevented apoptosis-related alterations in neonatal cardiomyocytes exposed to asphyxia [16,17] or oxidative stress [18]. …”

Section: Figmentioning

confidence: 99%

Spontaneous Hypothermia Is Not Able to Completely Counteract Cardiac Arrest-Induced Mitochondrial Impairment in the Rat Heart

Keilhoff

Ebmeyer²,

Schild

2012

Neonatology

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Vijlbrief et al. [Neonatology 2012;102:243–248] reported a beneficial effect of hypothermia on cardiac function after perinatal asphyxia indicated by low levels of B-type natriuretic peptide (BNP). Elevated troponin I plasma levels, however, reflects impairment of cardiomyocytes under hypothermic conditions. The importance of BNP and cardiac troponin I as biomarkers of cardiac dysfunction that may supplement or substitute Doppler echocardiography has been outlined. Using an asphyxia cardiac arrest (ACA) animal model under spontaneous hypothermia, we found a decrease in the activities of NADH-cytochrome c-oxidoreductase and succinate-cytochrome c-oxidoreductase in comparison to normothermic sham-operated controls. This observation indicates the impairment of the respiratory chain of heart mitochondria, which is accompanied by morphological changes in these mitochondria. Changed cardiac troponin I levels and respiratory chain complexes activity represent different but corresponding steps within the process of cardiomyocyte injury. Interestingly, liver and brain mitochondria remained unchanged under this condition. Patients could benefit from the control of mitochondrial function during hypothermic intervention. When indicated, substances could be supplemented that support mitochondrial function, e.g. antioxidative-acting vitamins and ubiquinone.

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Cyclosporine A prevents apoptosis-related mitochondrial dysfunction after neonatal cardioplegic arrest

Cited by 47 publications

References 35 publications

Gefitinib induces apoptosis in human glioma cells by targeting Bad phosphorylation

Gefitinib induces apoptosis in human glioma cells by targeting Bad phosphorylation

Comparison of various methods of ischaemic cardioprotection on vitality of rat heart grafts

Spontaneous Hypothermia Is Not Able to Completely Counteract Cardiac Arrest-Induced Mitochondrial Impairment in the Rat Heart

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