Hydrogen peroxide activation of cytosolic phospholipase A2 in vascular smooth muscle cells

Rao, Gadiparthi N.; Runge, M S; Alexander, R. Wayne

doi:10.1016/0167-4889(95)91997-z

Cited by 103 publications

(53 citation statements)

References 40 publications

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“…It is recognized that cPLA 2 is responsible for the immediate arachidonic acid release and PGE 2 production upon stimulation. In fact, H 2 O 2 is known to activate cPLA 2 to release arachidonic acid in other cell systems including vascular smooth muscle cells, striatal neurons, and fibroblasts (13,42,44). In the present study, we showed that the increase in arachidonic acid release stimulated by H 2 O 2 and the synergistic effect of H 2 O 2 and PDGF (see Fig.…”

Section: Discussionsupporting

confidence: 58%

ERK and p38 MAP kinase are involved in arachidonic acid release induced by H₂O₂and PDGF in mesangial cells

Hayama

Inoue

Akiba

et al. 2002

American Journal of Physiology-Renal Physiology

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-Increased prostaglandin production is implicated in the pathogenesis of glomerular disease. With this consideration, we examined the combined effects of reactive oxygen species and platelet-derived growth factor (PDGF), which might initiate glomerular dysfunction, on arachidonic acid release and cytosolic phospholipase A2 (cPLA2) activation in rat mesangial cells. H2O2-induced release of arachidonic acid was enhanced by PDGF, which by itself had little effect on the release, and the enhancement was completely inhibited by a cPLA2 inhibitor. The phosphorylation of cPLA2, extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein (MAP) kinase was upregulated by H2O2 or PDGF alone and except for ERK was enhanced further by the two in combination. The release of arachidonic acid induced by PDGF together with H2O2 was inhibited partially by an inhibitor of ERK or p38 MAP kinase and completely when the two inhibitors were combined; the inhibitory pattern was similar to that for the phosphorylation of cPLA2. These results suggest that the ERK and p38 MAP kinase pathways are involved in the increase in cPLA2 activation and arachidonic acid release induced by PDGF together with H2O2. hydrogen peroxide; p38 mitogen-activated protein kinase; extracellular signal-regulated kinase; cytosolic phospholipase A2; platelet-derived growth factor MESANGIAL CELLS SYNTHESIZE vasodilatory prostaglandins (PGs) such as PGE 2 , which act as relaxing factors and regulate glomerular hemodynamics under physiological conditions. However, an increase in renal PGE 2 production, which is observed in renal diseases such as glomerulonephritis and diabetic glomerulopathy, induces a functional disorder of the mesangium including abnormal glomerular filtration rate and is implicated in the pathogenesis of nephropathy (46,52).Previously, reactive oxygen species (ROS) such as hydrogen peroxide (H 2 O 2 ), superoxide anion, and hydroxyl radical were recognized to cause cell injury and therefore be involved in the pathogenesis of various diseases. However, recent observations indicate that ROS cause physiological responses other than pathological responses, including protein phosphorylation, Ca 2ϩ signaling, and the activation of transcription factors by stimulating intracellular signaling systems, thus suggesting that ROS function as second messengers in the signal transduction pathway stimulated by the proinflammatory cytokines interleukin-1␤ and tumor necrosis factor-␣ (21,36,38,50).In glomerular disorders, ROS are generated by several inflammatory cells including neutrophils, monocytes, and macrophages gathered in the inflamed glomeruli, and also by the mesangial cell itself (7, 9, 10). Previous studies revealed that the intracellular generation of ROS or exposure to H 2

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Section: Discussionsupporting

confidence: 58%

ERK and p38 MAP kinase are involved in arachidonic acid release induced by H₂O₂and PDGF in mesangial cells

Hayama

Inoue

Akiba

et al. 2002

American Journal of Physiology-Renal Physiology

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“…1 also shows that the treatment with GO induced the release of a small but significant amount of ArAc. This might be due to specific activation of CPLA2 via PKC and MAP kinase as previously reported [21].…”

Section: Resultssupporting

confidence: 68%

H₂O₂ renders cells accessible to lysis by exogenous phospholipase A₂: a novel mechanism for cell damage in inflammatory processes

et al. 1996

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Phospholipase A2 (PLA2) and H202, secreted from activated inflammatory cells, play a central role in the tissue damage occurring in inflammatory processes. However, while exogenous PLA2 alone does not cause cell lysis, it readily does so when acting with H202. We have found that H202 degrades cell surface proteoglycans, thus rendering the membrane PL accessible to hydrolysis by exogenous PLA2. This novel mechanism introduces a role for cell surface proteoglycans in protection of cells from damage by pro-inflammatory agents, and may assign a central role for the combined action of H202 and PLA2 in inflammatory and bacteriocidal processes.

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“…The observation that the cPLA 2 activity stimulated by peroxynitrite is inhibited by endogenously generated H 2 O 2 is an unexpected finding since the latter was previously described as a PLA 2 activator. [28][29][30] It is tempting to speculate that signalling events triggered by peroxynitrite, and leading to cPLA 2 activation, are intercepted by an inhibitory signalling triggered by H 2 O 2 . The possibility also exists that peroxynitrite and H 2 O 2 may cooperate in inducing ATP depletion, a condition recently reported to be associated with inhibition of cPLA 2 activity.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen peroxide generated at the level of mitochondria in response to peroxynitrite promotes U937 cell death via inhibition of the cytoprotective signalling mediated by cytosolic phospholipase A2

et al. 2004

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We have studied the relationships existing between delayed formation of H 2 O 2 and activation of cytosolic phospholipase A 2 (cPLA 2 ), events respectively promoting toxicity or survival in U937 cells exposed to peroxynitrite. The outcome of an array of different approaches using phospholipase A 2 inhibitors, or cPLA 2 antisense oligonucleotides, as well as specific respiratory chain inhibitors and respiration-deficient cells led to the demonstration that H 2 O 2 does not mediate toxicity by producing direct molecular damage. Rather, the effects of H 2 O 2 were found to be upstream to the arachidonic acid (AA)-mediated cytoprotective signalling and in fact causally linked to inhibition of cPLA 2 . Thus, it appears that U937 cells exposed to nontoxic concentrations of peroxynitrite are nevertheless committed to death, which however is normally prevented by the activation of parallel pathways resulting in cPLA 2 -dependent release of AA. A rapid necrotic response, however, takes place when high concentrations of peroxynitrite promote formation of H 2 O 2 at levels impairing the cPLA 2 cytoprotective signalling.

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Hydrogen peroxide activation of cytosolic phospholipase A2 in vascular smooth muscle cells

Cited by 103 publications

References 40 publications

ERK and p38 MAP kinase are involved in arachidonic acid release induced by H₂O₂and PDGF in mesangial cells

ERK and p38 MAP kinase are involved in arachidonic acid release induced by H₂O₂and PDGF in mesangial cells

H₂O₂ renders cells accessible to lysis by exogenous phospholipase A₂: a novel mechanism for cell damage in inflammatory processes

Hydrogen peroxide generated at the level of mitochondria in response to peroxynitrite promotes U937 cell death via inhibition of the cytoprotective signalling mediated by cytosolic phospholipase A2

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Hydrogen peroxide activation of cytosolic phospholipase A2 in vascular smooth muscle cells

Cited by 103 publications

References 40 publications

ERK and p38 MAP kinase are involved in arachidonic acid release induced by H2O2and PDGF in mesangial cells

ERK and p38 MAP kinase are involved in arachidonic acid release induced by H2O2and PDGF in mesangial cells

H2O2 renders cells accessible to lysis by exogenous phospholipase A2: a novel mechanism for cell damage in inflammatory processes

Hydrogen peroxide generated at the level of mitochondria in response to peroxynitrite promotes U937 cell death via inhibition of the cytoprotective signalling mediated by cytosolic phospholipase A2

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ERK and p38 MAP kinase are involved in arachidonic acid release induced by H₂O₂and PDGF in mesangial cells

ERK and p38 MAP kinase are involved in arachidonic acid release induced by H₂O₂and PDGF in mesangial cells

H₂O₂ renders cells accessible to lysis by exogenous phospholipase A₂: a novel mechanism for cell damage in inflammatory processes