Nonselective cation channels as effectors of free radical–induced rat liver cell necrosis

Barros, L. Felipe; Stutzin, Andrés; Calixto, Andrea; Catalán, M. y; Castro, Joel; Hetz, Claudio; Hermosilla, Tamara

doi:10.1053/jhep.2001.20530

Cited by 59 publications

(60 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As reported previously (Rose and Ransom, 1997) that in turn may contribute to the pathogenesis of injury (Chen et al, 1999;Barros et al, 2001;Aarts et al, 2003). To examine the contribution of Na ϩ influx through NSCCs to the rise in [Na ϩ ] i during anoxia, we applied Gd 3ϩ (Caldwell et al, 1998 (Fig.…”

Section: Voltage-activated Namentioning

confidence: 94%

Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

Sheldon

Diarra²,

Cheng³

et al. 2004

J. Neurosci.

View full text Add to dashboard Cite

Mechanisms that contribute to Na ϩ influx during and immediately after 5 min anoxia were investigated in cultured rat hippocampal neurons loaded with the Na ϩ -sensitive fluorophore sodium-binding benzofuran isophthalate. -dependent mechanism(s). The results provide insight into the intrinsic mechanisms that contribute to disturbed internal Na ϩ homeostasis during and immediately after anoxia in rat hippocampal neurons and, in this way, may play a role in the pathogenesis of anoxic or ischemic cell injury.

show abstract

Section: Voltage-activated Namentioning

confidence: 94%

Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

Sheldon

Diarra²,

Cheng³

et al. 2004

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The ROS-mediated necrotic volume increase and Na ϩ influx are suggested to be initiated by the binding of the free radicals to ion channels including nonselective Ca 2ϩ channels (10,83,84,105). The increased levels of Na ϩ activates Na ϩ -K ϩ -ATPase and consumes ATP, which further activates nonselective Ca 2ϩ channels, resulting in massive cytosolic Ca 2ϩ accumulation.…”

Section: Ca 2ϩ Accumulationmentioning

confidence: 99%

Cell death induced by acute renal injury: a perspective on the contributions of apoptosis and necrosis

Padanilam

2003

American Journal of Physiology-Renal Physiology

334

270

View full text Add to dashboard Cite

In humans and experimental models of renal ischemia, tubular cells in various nephron segments undergo necrotic and/or apoptotic cell death. Various factors, including nucleotide depletion, electrolyte imbalance, reactive oxygen species, endonucleases, disruption of mitochondrial integrity, and activation of various components of the apoptotic machinery, have been implicated in renal cell vulnerability. Several approaches to limit the injury and augment the regeneration process, including nucleotide repletion, administration of growth factors, reactive oxygen species scavengers, and inhibition of inducers and executioners of cell death, proved to be effective in animal models. Nevertheless, an effective approach to limit or prevent ischemic renal injury in humans remains elusive, primarily because of an incomplete understanding of the mechanisms of cellular injury. Elucidation of cell death pathways in animal models in the setting of renal injury and extrapolation of the findings to humans will aid in the design of potential therapeutic strategies. This review evaluates our understanding of the molecular signaling events in apoptotic and necrotic cell death and the contribution of various molecular components of these pathways to renal injury.

show abstract

“…[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. 15 For instance, in smooth muscle cells, the calcium release was inhibited by the previous discharge of inositol 1,4,5-trisphosphate (InsP 3 )-sensitive stores with vasopressin.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2004

View full text Add to dashboard Cite

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.

show abstract

Nonselective cation channels as effectors of free radical–induced rat liver cell necrosis

Cited by 59 publications

References 49 publications

Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

Cell death induced by acute renal injury: a perspective on the contributions of apoptosis and necrosis

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

Contact Info

Product

Resources

About