Redox Regulation of Signal Transduction in Smooth Muscle Cells: Distinct effects of PKC-down regulation and PKC inhibitors on oxidant induced MAP kinase

Taher, Mohiuddin M.; Mahgoub, Mahmoud A.; Abd‐Elfattah, Anwar S.

doi:10.3109/10799899809047743

Cited by 11 publications

(4 citation statements)

References 31 publications

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“…In further agreement with our results, oxidant-induced MAP kinase activation in VSMCs was found to be sensitive to genistein and tyrphostin and to bypass PKC. 35 Nonetheless, there is evidence that PKC activation might precede O 2 Ϫ generation 34 or that it transduces O 2 Ϫ signaling to ERK1/2, 36 although this was not the case in our setup. Differences in experimental models (organ versus cell culture) or in species could account for these disparities.…”

Section: Discussioncontrasting

confidence: 46%

Pulsatile Stretch–Induced Extracellular Signal–Regulated Kinase 1/2 Activation in Organ Culture of Rabbit Aorta Involves Reactive Oxygen Species

Lehoux

Esposito

Merval

et al. 2000

ATVB

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Abstract-Increased steady intraluminal pressure in blood vessels activates the extracellular signal-regulated kinase (ERK)1/2 pathway. However, signal transduction of pulsatile stretch has not been elucidated. Using an organ culture model of rabbit aorta, we studied ERK1/2 activation by pulsatility in vessels maintained at 80 mm Hg for 24 hours. ERK1/2 activity was evaluated by in-gel kinase assays and by Western blot. Compared with control aortas without pulsatility, aortas submitted to a pulsatile 10% variation in vessel diameter displayed a significant increase in ERK1/2 activity (207Ϯ12%, PϽ0.001), which remained high after removal of the endothelium. Unlike steady overstretch, pulsatile stretch-induced activation of ERK1/2 was not modified by herbimycin A, a Src family tyrosine kinase inhibitor, but was reduced by other tyrosine kinase inhibitors, tyrphostin A48 and genistein (162Ϯ27% and 144Ϯ14%, respectively). Conversely, ERK1/2 activity was markedly decreased in pulsatile vessels treated with staurosporine (114Ϯ18%) although neither of the more specific protein kinase C inhibitors, Ro-31-8220 or Gö-6976, blocked ERK1/2 activation (209Ϯ24% and 238Ϯ34%, respectively), whereas staurosporine had no effect on steady overstretch-induced ERK1/2 activation. Pulsatility induced superoxide anion generation, which was prevented by the NADPH oxidase inhibitor diphenyleneiodonium. Furthermore, polyethylene glycol-superoxide dismutase completely abolished ERK1/2 activation by pulsatility (114Ϯ12%). Finally, ERK1/2 and O 2 Ϫ levels in freshly isolated vessels were equivalent to the levels found in pulsatile vessels. In conclusion, pulsatile stretch activates ERK1/2 in the arterial wall via pathways different from those induced by steady overstretch. Pulsatility might be considered a physiological stimulus that maintains a certain degree of ERK1/2 activation via oxygen-derived free radical production. (Arterioscler Thromb Vasc

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Section: Discussioncontrasting

confidence: 46%

Pulsatile Stretch–Induced Extracellular Signal–Regulated Kinase 1/2 Activation in Organ Culture of Rabbit Aorta Involves Reactive Oxygen Species

Lehoux

Esposito

Merval

et al. 2000

ATVB

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“…This is in keeping with our data that the 4,4¢-DTDP-induced Ca 2+ release was prevented by pretreatment with a reducing agent in a concentration-dependent manner, and was fully reversed by addition of the reducing agent afterwards. Although oxidation by hydrogen peroxide has been shown to alter Ca 2+ signaling by activation of protein kinase C in (Tornquist et al 2000) and muscle cells (Taher et al 1998), our results suggest that 4,4¢-DTDPinduced Ca 2+ release in osteoblasts appears to be independent of protein kinase C activity. This discrepancy may reflect the differences in the species of oxidizing agents and cell types.…”

Section: Discussionmentioning

confidence: 68%

Sulfhydryl modification by 4,4?-dithiodipyridine induces calcium mobilization in human osteoblast-like cells

Kuo

Chen

et al. 2003

Archives of Toxicology

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The effect of oxidants on Ca 2+ movement in osteoblasts is unclear. In this study, we show that 4,4¢-dithiodipyridine (4,4¢-DTDP), a reactive disulphide that mobilizes Ca 2+ in muscle, induces an increase in cytoplasmic free-Ca 2+ concentrations ([Ca 2+ ] i ) in MG63 human osteosarcoma cells loaded with the Ca 2+ -sensitive dye fura-2. 4,4¢-DTDP acted in a concentrationdependent manner with an EC 50 of 10 lM. Removing extracellular Ca 2+ reduced the Ca 2+ signal by 35%. In Ca 2+ -free medium, the 4,4¢-DTDP-induced [Ca 2+ ] i increase was not changed by depleting store Ca 2+ with 50 lM brefeldin A (a Golgi apparatus permeabilizer), by 2 lM carbonylcyanide m-chlorophenylhydrazone (CCCP, a mitochondrial uncoupler), by 1 lM thapsigargin (an inhibitor of the endoplasmic reticulum Ca 2+ pump) or by 5 lM ryanodine. Ca 2+ signals induced by 4,4¢-DTDP in Ca 2+ -containing medium were not affected by modulation of protein kinase C activity or suppression of phospholipase C activity. However, 4,4¢-DTDP-induced Ca 2+ release was inhibited by a thiolselective reducing reagent, dithiothreitol (0.05-2.5 mM), in a concentration-dependent manner. Collectively, this study shows that 4,4¢-DTDP induced [Ca 2+ ] i increases in human osteosarcoma cells via releasing store Ca 2+ from multiple stores in a manner independent of protein kinase C or phospholipase C activity. The store Ca 2+ release induced by 4,4¢-DTDP appears to be associated with thiol oxidation. Furthermore, overnight incubation with 4,4¢-DTDP inhibited cell activity in a concentrationdependent manner.

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“…Sphingosine may alter the redox status of sulfhydryl groups of proteins, and the protein phosphatases may be inactivated by an oxidation mechanism (24). We have recently shown that the agents which oxidize sulfhydryl groups (N-ethylmaleimide and phenylarsine oxide) inhibited PKC while activating PLD and MAP kinase (24,(28)(29)(30). A similar mechanism may apply to sphingosine's actions for inhibiting PKC and activating PLD and MAP kinase; however, this remains to be established.…”

Section: As Shown Inmentioning

confidence: 99%

“…The MAP kinase assay was performed according to published procedure with slight modifications. The details of this method were described recently (28)(29)(30). In brief, growth arrested cells were incubated in DMEM for indicated time periods with various agents, then scraped into 0.5 ml of homogenization buffer 50 mM Tris-HC1 (pH 7.5), 2.0 mM EGTA, 1.0 mM DTT, 0.2 mM phenyl methyl sulfonylfluoride, 10 mM 13-glycerophosphate, 1 mM sodium orthovanadate and 0.12 U/ml aprotinin, 1.0 t~g/ml leupeptin.…”

Section: Methodsmentioning

confidence: 99%

Sphingosine induces phospholipase D and mitogen activated protein kinase in vascular smooth muscle cells

1998

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: The enzymes phospholipase D and diacylglycerol kinase generate phosphatidic acid which is considered to be a mitogen. Here we report that sphingosine produced a significant amount of phosphatidic acid in vascular smooth muscle ceils from the rat aorta. The diacylglycerol kinase inhibitor R59 949 partially depressed sphingosine induced phosphatidic acid formation, suggesting that activation of phospholipase C and diacylglycerol kinase can not account for the bulk of phosphatidic acid produced and that additional pathways such as phospholipase D may contribute to this. Further, we have shown that phosphatidylethanol was produced by sphingosine when vascular smooth muscle cells were stimulated in the presence of ethanol. Finally, as previously shown for other cell types, sphingosine stimulated mitogen-activated protein kinase in vascular smooth muscle cells.

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Redox Regulation of Signal Transduction in Smooth Muscle Cells: Distinct effects of PKC-down regulation and PKC inhibitors on oxidant induced MAP kinase

Cited by 11 publications

References 31 publications

Pulsatile Stretch–Induced Extracellular Signal–Regulated Kinase 1/2 Activation in Organ Culture of Rabbit Aorta Involves Reactive Oxygen Species

Pulsatile Stretch–Induced Extracellular Signal–Regulated Kinase 1/2 Activation in Organ Culture of Rabbit Aorta Involves Reactive Oxygen Species

Sulfhydryl modification by 4,4?-dithiodipyridine induces calcium mobilization in human osteoblast-like cells

Sphingosine induces phospholipase D and mitogen activated protein kinase in vascular smooth muscle cells

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