Effect of hydrogen peroxide on calcium homeostasis in smooth muscle cells

Roveri, Antonella; Coassin, Mariagrazia; Maiorino, Matilde; Zamburlini, Adriana; Amsterdam, F. T. M. Van; Ratti, Emiliangelo; Ursini, Fulvio

doi:10.1016/0003-9861(92)90671-i

Cited by 152 publications

(80 citation statements)

References 13 publications

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“…Cell Culture-The rat thoracic aorta smooth muscle cell line A7r5 and the rat myoblast H9c2 cell line were grown in Dulbecco's modified Eagle's medium as described (29,30) but supplemented with 50 nM sodium selenite.…”

Section: Methodsmentioning

confidence: 99%

Distinct Promoters Determine Alternative Transcription of gpx-4 into Phospholipid-Hydroperoxide Glutathione Peroxidase Variants

Maiorino

Scapin

Ursini

et al. 2003

Journal of Biological Chemistry

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114

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A nuclear variant of phospholipid-hydroperoxide glutathione peroxidase (PHGPx, GPx-4) was considered to be derived from alternative pre-mRNA splicing in testis and to regulate sperm maturation. The genomic sequence of rat gpx-4 was established and investigated in respect to expression into the cytosolic, mitochondrial, and nuclear forms of PHGPx. In silico analysis suggested the presence of two distinct promoter regions, the upstream one leading to transcripts translating into cPHGPx or mPHGPx and the downstream one yielding nPHGPx. The promoter activity of both regions was verified by luciferase-based reporter constructs in A7r5 and H9c2 cells. The data reveal that the formation of nPHGPx is due to alternative transcription and not to alternative splicing. Transcripts encoding nPHGPx were most abundant in testis although not restricted to this organ. This observation points to a general role of the nuclear PHGPx variant in regulating cell division.

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Section: Methodsmentioning

confidence: 99%

Distinct Promoters Determine Alternative Transcription of gpx-4 into Phospholipid-Hydroperoxide Glutathione Peroxidase Variants

Maiorino

Scapin

Ursini

et al. 2003

Journal of Biological Chemistry

Self Cite

114

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“…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. 12 In contrast, in insulin-secreting cells the calcium rise was not affected by previous depletion of thapsigargin-sensitive stores. 1 In pancreatic acinar cells, it was concluded that calcium is released from both thapsigargin-sensitive stores and the mitochondria.…”

Section: Introductionmentioning

confidence: 94%

“…[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

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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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“…It has been commonly indicated that ROS cause a rapid increase in cytoplasmic Ca ++ concentration in diverse cell types (Roveri et al, 1992) (Chakraborti et al, 1999) (Okabe et al, 2000), which can contribute to the early transient calpain activation. However, the current study indicated that the full activity of calpain did not occur until a later timepoint that follows the early wave of oxidative damage and the peak of mitochondrial dysfunction (Singh et al, 2006).…”

Section: Interaction Of Peroxynitrite-induced Oxidative and Calpain-mmentioning

confidence: 99%

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

Deng

Thompson

Gao

et al. 2007

Experimental Neurology

132

171

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We assessed the temporal and spatial characteristics of PN-induced oxidative damage and its relationship to calpain-mediated cytoskeletal degradation and neurodegeneration in a severe unilateral controlled cortical impact (CCI) traumatic brain injury (TBI) model. Quantitative temporal time-course studies were performed to measure two oxidative damage markers: 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE) at 30 min, 1, 3, 6, 12, 24, 48, 72 hrs, 7 days after injury in ipsilateral cortex of young adult male CF-1 mice. Secondly, the time course of Ca ++ -activated, calpain-mediated proteolysis was also analyzed using quantitative western-blot measurement of breakdown products of the cytoskeletal protein α-spectrin. Finally, the time course of neurodegeneration was examined using de Olmos silver staining. Both oxidative damage markers increased in cortical tissue immediately after injury (30 min) and elevated for the first 3-6 hrs before returning to baseline. In the immunostaining study, the PN-selective marker, 3NT, and the lipid peroxidation marker, 4HNE, were intense and overlapping in the injured cortical tissue. α-Spectrin breakdown products, which was used as biomarker for calpain-mediated cytoskeletal degradation, were also increased after injury, but the time course lagged behind the peak of oxidative damage and did not reach its maximum until 24 hrs post-injury. In turn, cytoskeletal degradation preceded the peak of neurodegeneration which occurred at 48 hrs post-injury. These studies have led us to the hypothesis that PN-mediated oxidative damage is an early event that contributes to a compromise of Ca ++ homeostatic mechanisms which causes a massive Ca ++ overload and calpain activation which is a final common pathway that results in post-traumatic neurodegeneration.

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Effect of hydrogen peroxide on calcium homeostasis in smooth muscle cells

Cited by 152 publications

References 13 publications

Distinct Promoters Determine Alternative Transcription of gpx-4 into Phospholipid-Hydroperoxide Glutathione Peroxidase Variants

Distinct Promoters Determine Alternative Transcription of gpx-4 into Phospholipid-Hydroperoxide Glutathione Peroxidase Variants

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

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

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