Role of intracellular calcium in hydrogen peroxide-induced renal tubular cell injury

Ueda, Norishi; Shah, Sudhir V.

doi:10.1152/ajprenal.1992.263.2.f214

Cited by 42 publications

(51 citation statements)

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“…11 In this paper, we did not investigate the events lying downstream of calcium, but in the light of previous data in other systems, several mechanisms of injury may be proposed. In HeLa cells exposed to peroxide, the mitochondria became calcium-loaded, a phenomenon that in neurons mediates glutamate excitotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 The early phase of calcium overload is important for cell death as its suppression by increasing calcium buffering greatly reduced DNA degradation, 6 mitochondrial damage, [6][7][8][9] activation of surface nonselective cation channels, 1,10 apoptosis 5,6,9 and necrosis. [6][7][8]10,11 Despite its pathophysiological relevance, the source of oxidative calcium has proved elusive. Whereas all studies in non-neuronal cells have discarded an extracellular origin, 1,[12][13][14] the participation of specific calcium storage compartments is unclear.…”

Section: Introductionmentioning

confidence: 99%

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A cytosolic source of calcium unveiled by hydrogen peroxide with relevance for epithelial cell death

et al. 2004

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Oxidative stress releases intracellular calcium, which plays a pathogenic role in mammalian cell death. Here we report a search for the source of oxidative calcium in HeLa cells based on confocal epifluorescence microscopy. H 2 O 2 caused a rapid increase in cytosolic calcium, which was followed by mitochondrial Ca 2 þ loading. Combined mitochondrial uncoupling with full depletion of thapsigargin-sensitive stores abrogated inositol 1,4,5-trisphosphate-mediated calcium release but failed to inhibit H 2 O 2 -induced calcium release, observation that was confirmed in MDCK cells. Prevention of peroxide-induced acidification with a pH clamp was also ineffective, discarding a role for endosomal/lysosomal Ca 2 þ / H þ exchange. Lysosomal integrity was not affected by H 2 O 2 . Mature human erythrocytes also reacted to peroxide by releasing intracellular calcium, thus directly demonstrating the cytosolic source. Glutathione depletion markedly sensitized cells to H 2 O 2 , an effect opposite to that achieved by DTT. Iron chelation was ineffective. In summary, our results show the existence of a previously unrecognized sulfhydrylsensitive source of pathogenic calcium in the cytosol of mammalian cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A cytosolic source of calcium unveiled by hydrogen peroxide with relevance for epithelial cell death

et al. 2004

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“…H 2 O 2 and t-butylhydroperoxide have been extensively used as oxidative agents in studying mechanism of renal cell injury by acute oxidative stress (Schnellmann 1988;Walker & Shah 1991;Ueda & Shah 1992). However, a number of studies have shown remarkable differences between the effects of H 2 O 2 and those of t-butylhydroperoxide in various cell types (Starke & Farber 1985;Baker & He 1991;Yamamoto et al 1993;Guidarelli et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Oxidant‐Induced Cell Death in Renal Epithelial Cells: Differential Effects of Inorganic and Organic Hydroperoxides

Park

Jung

Koak

et al. 2003

Pharmacology & Toxicology

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This study was undertaken in order to examine the roles of lipid peroxidation and poly (ADP-ribose) polymerase (PARP) activation in oxidant-induced renal cell death. Opossum kidney cell cultures were used as the renal epithelial cell model, and an inorganic hydroperoxide H 2 O 2 and an organic hydroperoxide t-butylhydroperoxide were employed as model oxidants. Cell death by both oxidants could be prevented by thiols (dithiothreitol and glutathione), iron chelators (deferoxamine and phenanthroline), and hydroxyl radical scavengers (dimethylthiourea and pyruvate). Phenolic antioxidants N,Nø-diphenyl-p-phenylenediamine (DPPD) and butylated hydroxyanisole had no effect on the H 2 O 2 -induced cell death . However, the t-butylhydroperoxide-induced cell death was effectively prevented by these antioxidants. The PARP inhibitor 3-aminobenzamide prevented the cell death induced by H 2 O 2 , but not cell death by t-butylhydroperoxide. The PARP activity was increased in cells exposed to H 2 O 2 but not t-butylhydroperoxide. Unlike in opossum kidney cells, in rabbit renal cortical slices both oxidants H 2 O 2 and t-butylhydroperoxide induced cell death through a lipid peroxidation-dependent and PARP-independent mechanism. Effects of DPPD and 3-aminobenzamide on H 2 O 2 -induced cell death in primary cultured rabbit proximal tubular cells were similar to those in opossum kidney cells. These results indicate that 1) the H 2 O 2 -induced cell death in cultured renal epithelial cells is associated with PARP activation but not lipid peroxidation, whereas the t-butylhydroperoxide-induced cell death is mediated by lipid peroxidation, and 2) the role of lipid peroxidation in H 2 O 2 cytotoxicity may be different between freshly isolated renal tubular cells and cultured renal epithelial cells.

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“…Tubular epithelial cells in primary culture displayed strong alkaline phosphatase reactivity and were identified by mAbs for cytokeratin (Labsystems, Helsinki, Finland), which are markers of proximal tubules (30). After reaching confluence, tubular epithelial cells (1 ϫ 10 7 /10-cm dish) were washed with PBS and were exposed to 5 mM H 2 O 2 (31,32) in DMEM. These cells were also exposed to 1, 10, and 100 ng/ml MK in DMEM.…”

Section: H 2 O 2 -Mediated Oxidant Injury Modelmentioning

confidence: 99%

Midkine Is Involved in Neutrophil Infiltration into the Tubulointerstitium in Ischemic Renal Injury

Sato

Kadomatsu

Yuzawa³

et al. 2001

The Journal of Immunology

169

193

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Midkine (MK) is a multifunctional heparin-binding protein and promotes migration of neutrophils, macrophages, and neurons. In the normal mouse kidney, MK is expressed in the proximal tubules. After renal ischemic reperfusion injury, its expression in proximal tubules was increased. Immediate increase of MK expression was found when renal proximal tubular epithelial cells in culture were exposed to 5 mM H2O2. Histologically defined tubulointerstitial damage was less severe in MK-deficient (Mdk−/−) than in wild-type (Mdk+/+) mice at 2 and 7 days after ischemic reperfusion injury. Within 2 days after ischemic injury, inflammatory leukocytes, of which neutrophils were the major population, were recruited to the tubulointerstitium. The numbers of infiltrating neutrophils and also macrophages were lower in Mdk−/− than in Mdk+/+ mice. Induction of macrophage inflammatory protein-2 and macrophage chemotactic protein-1, chemokines for neutrophils and macrophages, respectively, were also suppressed in Mdk−/− mice. Furthermore, renal tubular epithelial cells in culture expressed macrophage inflammatory protein-2 in response to exogenous MK administration. These results suggested that MK enhances migration of inflammatory cells upon ischemic injury of the kidney directly and also through induction of chemokines, and contributes to the augmentation of ischemic tissue damage.

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Role of intracellular calcium in hydrogen peroxide-induced renal tubular cell injury

Cited by 42 publications

References 0 publications

A cytosolic source of calcium unveiled by hydrogen peroxide with relevance for epithelial cell death

A cytosolic source of calcium unveiled by hydrogen peroxide with relevance for epithelial cell death

Oxidant‐Induced Cell Death in Renal Epithelial Cells: Differential Effects of Inorganic and Organic Hydroperoxides

Midkine Is Involved in Neutrophil Infiltration into the Tubulointerstitium in Ischemic Renal Injury

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