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Kharbangar, A.; Khynriam, Dimos; Prasad, Surendra

doi:10.1023/a:1007648427024

Cited by 31 publications

(4 citation statements)

References 44 publications

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“…For example, cisplatin nephrotoxicity induces a significant decrease of cytochrome c oxidase (COX) activity and a reduction in COX IV protein expression in the proximal tubules 16 . Furthermore, cisplatin treatment reduces mitochondrial MnSOD 17 , coupled with decreases in glutathione and succinate dehydrogenase (SDH) activity 18 , resulting in drastic decreases in antioxidant activity and ROS production from mitochondria. By using multiphoton microscopy, Hall and colleagues examined mitochondrial function in vivo during renal ischemia-reperfusion injury and demonstrated a marked increase in mitochondrial nicotinamide adenine dinucleotide (NADH) and the dissipation of mitochondrial membrane potential (ΔΨm) in proximal tubules, but not distal tubules 19 .…”

Section: Energy Metabolism Solute Transport and Sepsismentioning

confidence: 99%

Mitochondrial Function and Disturbances in the Septic Kidney

Parikh

Yang

et al. 2015

Seminars in Nephrology

151

123

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Per milligram of tissue, only the heart exceeds the kidney’s abundance of mitochondria. Not surprisingly, renal mitochondria are most densely concentrated in the epithelium of the nephron, at sites where the chemical work of moving solutes against electrochemical gradients places large and constant demands for ATP. Derangements of renal epithelial mitochondria appear to be a hallmark for diverse forms of acute kidney injury (AKI). The pathogenesis of multiple-organ dysfunction syndrome (MODS) in sepsis is complex, but a substantial body of experimental and observational human data supports the twin concepts that mitochondrial dysfunction contributes to impaired filtration and that recovery of mitochondrial structure and function is essential for recovery from sepsis-associated AKI. These insights have suggested novel methods to diagnose, stratify, prevent, or even treat this common and deadly complication of critical illness. This review will (1) describe the structure and functions of healthy mitochondria and how renal energy metabolism relates to solute transport; (2) provide an overview of the evidence linking mitochondrial pathology to renal disease; (3) summarize the mitochondrial lesions observed in septic AKI; (4) analyze the role of mitochondrial processes including fission/fusion, mitophagy, and biogenesis in the development of septic AKI and the recovery from this disease; and (5) explore the potential for therapeutically targeting mitochondria to prevent or treat septic AKI.

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Section: Energy Metabolism Solute Transport and Sepsismentioning

confidence: 99%

Mitochondrial Function and Disturbances in the Septic Kidney

Parikh

Yang

et al. 2015

Seminars in Nephrology

151

123

View full text Add to dashboard Cite

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“…These defects in respiratory chain lead to ROS production from mitochondria. Furthermore, cisplatin treatment reduces mitochondrial MnSOD [12], coupled with decreases in glutathione and succinate dehydrogenase (SDH) activity [13], resulting in drastic decreases in the antioxidant activity in kidney cells. In line with these observations, in cisplatin-treated renal tubular cells mitochondria show a decrease of mitochondrial mass, disruption of cristae, and extensive mitochondrial swelling in late stage [14], which are associated with significant reductions in mitochondrial activity and ATP production.…”

Section: Mitochondrial Dysregulation In Cisplatin Nephrotoxicitymentioning

confidence: 99%

Mitochondrial dysregulation and protection in cisplatin nephrotoxicity

et al. 2014

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Nephrotoxicity is a major side effect of cisplatin in chemotherapy. Pathologically, cisplatin nephrotoxicity is characterized by cell injury and death in renal tubules. The research in the past decade has gained significant understanding of the cellular and molecular mechanisms of tubular cell death, revealing a central role of mitochondrial dysregulation. The pathological changes of mitochondria in cisplatin nephrotoxicity are mainly triggered by DNA damage response, pro-apoptotic protein attack, disruption of mitochondrial dynamics, and oxidative stress. As such, inhibitory strategies targeting these cytotoxic events may provide renal protection. Nonetheless, ideal approaches for renoprotection should not only protect kidneys but also enhance the anti-cancer efficacy of cisplatin in chemotherapy.

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“…ROS is generated in mitochondria when cells are exposed to environmental stress including cisplatin challenge [6, 7]. Excessive accumulation of ROS causes DNA damage and subsequently activates apoptotic machinery for cell death.…”

Section: Introductionmentioning

confidence: 99%

Glutathione Peroxidase 1 Promotes NSCLC Resistance to Cisplatin via ROS-Induced Activation of PI3K/AKT Pathway

Chen

Shen

et al. 2019

BioMed Research International

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Purpose. Reactive oxygen species (ROS)-induced cytotoxicity is an important mechanism by which cisplatin kills tumor cells. Glutathione peroxidase family (GPXs) is an important member of antioxidant system which metabolizes intracellular ROS and maintains homeostasis of cells. Altered expressions of GPXs enzymes, especially GPX1, have been described in a variety of human cancers. However, their functional roles in cisplatin-based chemoresistance in human malignancies including non-small cell lung cancer have never been explored. Methods. A panel of NSCLC cell lines were selected for this study. GPX1 expression was detected using quantitative RT-PCR and Western blot. Cisplatin-induced cell killing was analyzed by CCK8 assay. Intracellular ROS levels were detected by fluorescence-based flow cytometry analysis. In vitro overexpression and knockdown of GPX1 expression were performed using GPX1 expression vector and siRNA approaches. Protein levels of PTEN, NF-κB, BCL2, Bax, and phosphorylated AKT were detected with western blot analysis using specific antibodies. Results. GPX1 expression was upregulated in a subset of NSCLC cell lines resistant to cisplatin treatment. Expression vector-mediated forced overexpression of GPX1 significantly increased cisplatin resistance in NSCLC cell lines, whereas RNA inference-mediated downregulation of GPX1 could restore sensitivity to cisplatin. Overexpression of GPX1 significantly suppressed elevation of intracellular ROS and activation of AKT pathway when NSCLC cell lines were exposed to different concentrations of cisplatin. Activation of the AKT pathway inhibited proapoptotic cascade and subsequently led to cisplatin resistance in NSCLC cells. Inhibition of NF-κB by its chemical inhibitor BAY can significantly downregulate GPX1 expression and restore the cisplatin sensitivity of the cell lines resistant to cisplatin. Conclusions. Our findings suggested that overexpression of GPX1 is a novel molecular mechanism for cisplatin-based chemoresistance in NSCLC. GPX1 overexpression blocks cisplatin-induced ROS intracellular accumulation, activates PI3K-AKT pathway by increased AKT phosphorylation, and further leads to cisplatin resistance in NSCLC cells. Inhibition of NF-κB signaling may be an alternative approach for restoring cisplatin sensitivity for NSCLC cells resistant to cisplatin-based chemotherapy.

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Cited by 31 publications

References 44 publications

Mitochondrial Function and Disturbances in the Septic Kidney

Mitochondrial Function and Disturbances in the Septic Kidney

Mitochondrial dysregulation and protection in cisplatin nephrotoxicity

Glutathione Peroxidase 1 Promotes NSCLC Resistance to Cisplatin via ROS-Induced Activation of PI3K/AKT Pathway

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