High glucose-induced Ca2+ overload and oxidative stress contribute to apoptosis of cardiac cells through mitochondrial dependent and independent pathways

Kumar, Sandeep; Kain, Vasundhara; Sitasawad, Sandhya L.

doi:10.1016/j.bbagen.2012.02.010

Cited by 80 publications

(72 citation statements)

References 60 publications

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“…Study has shown that hypothermia result in impaired mitochondrial bioenergetics, and myocardial ROS increases in proportion to a cold-induced alteration of mitochondrial bioenergetics (Camara et al, 2004). Intracellular calcium overload can induce mitochondrial oxidative phosphorylation disorders; decreased mitochondrial membrane potential; decreased tissue ATP content; cytoplasmic phospholipase; and protease activation, which can lead to irreversible damage to cell (Kumar et al, 2012). Our current study confirmed intracellular calcium overload was involved in cell damage that induced by hypothermal stimulation.…”

Section: Discussionsupporting

confidence: 89%

ERK5 knock down aggravates detrimental effects of hypothermal stimulation on cardiomyocytes via Bim upregulation

Wang

Zhou²,

Liang

et al. 2013

Environmental Toxicology and Pharmacology

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Section: Discussionsupporting

confidence: 89%

ERK5 knock down aggravates detrimental effects of hypothermal stimulation on cardiomyocytes via Bim upregulation

Wang

Zhou²,

Liang

et al. 2013

Environmental Toxicology and Pharmacology

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“…5A and 5C). The mitochondrial apoptotic pathway is involved in oxidative stress-induced cell apoptosis [30-32]. To verify the role of PA-induced mitochondrial ROS production in the mitochondrial apoptotic pathway, differentiated podocytes were pre-incubated with the mitochondrial antioxidant, mitoTEMPO (100 nM) for 1 h and then treated with PA (150 μM) for 24 h. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Palmitic Acid-Induced Podocyte Apoptosis via the Reactive Oxygen Species-Dependent Mitochondrial Pathway

Liu

Chen

Sun

et al. 2018

Kidney Blood Press Res

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Background/Aims: Chronic kidney disease (CKD) is often accompanied by hyperlipidemia, which accelerates progression of the disease. Podocyte injury can lead to dysfunction of the glomerular filtration barrier, which is associated with proteinuria, a risk marker for the progression of CKD. Our previous studies demonstrated that palmitic acid (PA) can induce podocyte apoptosis; however, the underlying mechanisms are unclear. In the present study, we investigated the specific molecular mechanisms of PA-induced apoptosis in cultured podocytes. Methods: We cultured mouse podocytes and treated them with PA. Then, cell viability was measured using the Cell Counting Kit-8 colorimetric assay, lipid uptake was assessed by Oil Red O staining and boron-dipyrromethene staining, apoptosis was measured by flow cytometry, mitochondrial injury was assessed by JC-1 staining and transmission electron microscopy, and mitochondrial production of reactive oxygen species (ROS) was evaluated by fluorescence microscopy using the MitoSOX Red reagent. The effects of PA on the mitochondria-mediated caspase activation pathway were investigated by examining the expression of caspase-8, cleaved caspase-9, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl-2), Bax, Bid, cytochrome c, and Fas-associated protein with death domain (FADD) using western blotting. The translocation of Bax and cytochrome c were detected by immunofluorescence. Results: PA treatment significantly increased lipid accumulation and induced podocyte apoptosis. We investigated whether the two primary apoptosis signaling pathways (death receptor-mediated pathway and mitochondria-mediated pathway) were involved in the execution of PA-induced podocyte apoptosis, and found that the levels of FADD, caspase-8, and Bid did not significantly change during this process. Meanwhile, PA treatment induced an increase in Bax protein expression and a decrease in Bcl-2 protein expression, with Bax translocation to the mitochondria. Furthermore, PA treatment induced mitochondrial impairment, and triggered the release of cytochrome c from the mitochondria to cytosol, with a concomitant dose-dependent increase in the levels of cleaved caspase-9, cleaved caspase-3, and PARP. Meanwhile, PA treatment increased mitochondrial production of ROS, and the mitochondria-targeted antioxidant mitoTEMPO significantly ameliorated PA-induced podocyte apoptosis. Conclusion: Our findings indicated that PA induced caspase-dependent podocyte apoptosis through the mitochondrial pathway, and mitochondrial ROS production participated in this process, thus potentially contributing to podocyte injury

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“…However, the calcium threshold to activate calpain is dramatically decreased during oxidative stress [51,52]. Ischemia-reperfusion damages the mitochondrial respiratory chain and markedly increases the ROS generation [53][54][55][56].…”

Section: Regulation Of Mitochondrial Calpain Activitymentioning

confidence: 99%

Heart mitochondria and calpain 1: Location, function, and targets

Chen¹,

Lesnefsky²

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Calpain 1 is an ubiquitous Ca(2+)-dependent cysteine protease. Although calpain 1 has been found in cardiac mitochondria, the exact location within mitochondrial compartments and its function remain unclear. The aim of the current review is to discuss the localization of calpain 1 in different mitochondrial compartments in relationship to its function, especially in pathophysiological conditions. Briefly, mitochondrial calpain 1 (mit-CPN1) is located within the intermembrane space and mitochondrial matrix. Activation of the mit-CPN1 within intermembrane space cleaves apoptosis inducing factor (AIF), whereas the activated mit-CPN1 within matrix cleaves complex I subunits and metabolic enzymes. Inhibition of the mit-CPN1 could be a potential strategy to decrease cardiac injury during ischemia-reperfusion.

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High glucose-induced Ca2+ overload and oxidative stress contribute to apoptosis of cardiac cells through mitochondrial dependent and independent pathways

Cited by 80 publications

References 60 publications

ERK5 knock down aggravates detrimental effects of hypothermal stimulation on cardiomyocytes via Bim upregulation

ERK5 knock down aggravates detrimental effects of hypothermal stimulation on cardiomyocytes via Bim upregulation

Palmitic Acid-Induced Podocyte Apoptosis via the Reactive Oxygen Species-Dependent Mitochondrial Pathway

Heart mitochondria and calpain 1: Location, function, and targets

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