[14] Modifications of cysteine-rich regions in protein kinase C induced by oxidant tumor promoters and enzyme-specific inhibitors

Gopalakrishna, Rayudu; Chen, Zhen-Hai; Gundimeda, Usha

doi:10.1016/0076-6879(95)52016-3

Cited by 49 publications

(29 citation statements)

References 28 publications

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“…RTKs are also involved in the activation of protein kinase C (PKC) via phospholipase C or PI3K, which has been shown to increase Akt activation (32) and cell proliferation of gliomas (33). All the three kinases, RTKs, MAPK and PKC, may be activated by ROS and inhibited by antioxidants (34)(35)(36). To find out if the inhibition of those intracellular pathways could have any antiproliferative effect in our experimental model, we used inhibitors of ERK1/2 and PKC pathways: PD98059 and calphostin C, respectively.…”

Section: Resultsmentioning

confidence: 99%

Intracellular Signaling Pathways Involved in the Cell Growth Inhibition of Glioma Cells by Melatonin

Martı́n¹,

Herrera²,

et al. 2006

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Melatonin is an indolamine mostly produced in the pineal gland, soluble in water, and highly lipophilic, which allows it to readily cross the blood-brain barrier. Melatonin possesses antioxidant properties and its long-term administration in rodents has not been found to cause noteworthy side effects. In the present work, we found that millimolar concentrations of this indolamine reduced cell growth of C6 glioma cells by 70% after 72 hours of treatment, inhibiting cell progression from G 1 to S phase of the cell cycle. Intraperitoneal administration of 15 mg/kg body weight of melatonin to rats previously injected in the flank with C6 glioma cells reduces tumor growth by 50% 2 weeks after the implant. Inhibition of cell growth does not depend on melatonin membrane receptor activation whereas it seemingly relates to the reduction of intracellular basal free radical levels by 30%. Increase of basal redox state of the cells and constitutive activation of tyrosine kinase receptor [receptor tyrosine kinase (RTK)] pathways, including the extracellular signal-regulated kinase 1/2 (ERK1/2) and the Akt and protein kinase C (PKC) signaling pathways, contribute to the progression of the gliomas leading to the constitutive activation of the redox-dependent survival transcription factor nuclear factor KB (NF-KB). The antioxidant effect of melatonin in C6 cells is associated to inhibition of NF-KB and Akt, but not of ERK1/2. The antiproliferative effect of the indolamine on these cells is partially abolished when coincubated with the PKC activator 12-O-tetradecanoylphorbol-13-acetate, thus indicating that the ability of melatonin to change cellular redox state may be inactivating the pathway RTK/PKC/ Akt/NF-KB. (Cancer Res 2006; 66(2): 1081-8)

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Section: Resultsmentioning

confidence: 99%

Intracellular Signaling Pathways Involved in the Cell Growth Inhibition of Glioma Cells by Melatonin

Martı́n¹,

Herrera²,

et al. 2006

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“…The results show that silica is able to induce translocation of PKC␣ and PKC⑀ from the cytosol to the membrane and stimulate PKC activity. With regard to the mechanism of silica-induced PKC activation, it may be noted that the structural aspects of PKC, the cysteine residues present within the regulatory and catalytic domains, make them very sensitive targets for ROS (19,34). PKCs can be activated and inactivated as an effective on/off signaling for several cellular mechanisms involved in signal transduction regulating cell proliferation or growth promotion.…”

Section: Discussionmentioning

confidence: 99%

“…2A). This transient translocation of PKC⑀ may be due to the degradation and/or selective modification of cysteine-rich regions of this isozyme (17,19,37,38). In our studies we used 12-O-tetradecanoylphorbol-13-acetate (TPA) as a positive control for PKC␣ and PKC⑀ membrane translocation assay, which is reported to cause a significant activation of these PKC subtypes in JB6 cells (24,25).…”

Section: Silica-induces Pkc Membrane Translocationmentioning

confidence: 99%

“…To address this question, we used several PKC inhibitors to investigate their effects on silica-induced phosphorylation of ERKs and p38 kinase. Among these inhibitors, RO-32-0432 is a selective inhibitor for PKC␣, whereas bisindolylmaleimide I and calphostin C are general inhibitors for most subtypes (4,19,30,50). Our results indicate that RO-32-0432, at concentrations of 25 and 50 nM, inhibited activation of both ERKs and p38 activation induced by silica (Fig.…”

Section: Silica-induces Pkc Membrane Translocationmentioning

confidence: 99%

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Involvement of protein kinase C in crystalline silica-induced activation of the MAP kinase and AP-1 pathway

Ding¹,

Huang²,

Lu³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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Crystalline silica has long been well established as a fibrogenic agent, and recent evidence has implicated it as a potential human carcinogen. However, the mechanisms of silica-induced disease development and progression are not well understood. Our previous studies demonstrated that crystalline silica is able to activate activator protein-1 (AP-1) through mitogen-activated protein kinase (MAPK) pathways. The present study investigates the possible involvement of protein kinase C (PKC) in silica-induced activation of the MAPK/AP-1 signal transduction pathway. Treatment of mouse epidermal cells (JB6 cell line) with freshly fractured silica stimulated translocation of PKC␣ and PKC⑀ from the cytosol to the membrane and activated AP-1 transcription activity. Pretreatment of cells with PKC inhibitors, including RO-32-0432, calphostin C, and bisindolylmaleimide I, inhibited silica-induced AP-1 activation and phosphorylation of ERKs and p38 kinase. These inhibitory effects by PKC inhibitors were dose dependent. Furthermore, overexpression of dominant negative mutant (DNM) of PKC␣ or PKC⑀ markedly blocked AP-1 activation as well as phosphorylation of ERKs and p38 kinase induced by freshly fractured silica. These results demonstrate that PKC␣ and PKC⑀ are essential in silica-induced AP-1 activation through the MAP kinase (ERKs and p38 kinases) pathway.

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“…One of the first studies to examine the role of oxidation on PKC activity clearly shows that treatments with low levels of the oxidant periodate modified the regulatory domain of PKC resulting in a loss of PKC activity while treatment with higher concentrations modified the catalytic domain resulting in an increase of PKC activity [52]. Later studies have reported that exposure to redox active compounds such as hydrogen peroxide [54], organic peroxides [36], and selenocompounds [53] result in the direct oxidation of PKC and change its activity. PKCs are a large family serine/threonine protein kinases subdivided into three subtypes based on their requirements for activation and are ubiquitously expressed [120].…”

Section: Redox Regulation Of Protein Kinase Cmentioning

confidence: 99%

Regulation of smooth muscle by inducible nitric oxide synthase and NADPH oxidase in vascular proliferative diseases

Ginnan

Guikema

Halligan

et al. 2008

Free Radical Biology and Medicine

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Inflammation plays a critical role in promoting smooth muscle migration and proliferation during vascular diseases such as post-angioplasty restenosis and atherosclerosis. Another common feature of many vascular diseases is the contribution of reactive oxygen (ROS) and nitrogen (RNS) species to vascular injury. Primary sources of ROS and RNS in smooth muscle are several isoforms of NADPH oxidase (Nox) and the cytokine-regulated inducible nitric oxide (NO) synthase (iNOS). One important example of the interaction between NO and ROS is the reaction of NO with superoxide to yield peroxynitrite, which may contribute to the pathogenesis of hypertension. In this review, we discuss the literature that supports an alternate possibility: Nox-derived ROS modulate NO bioavailability by altering the expression of iNOS. We highlight data showing co-expression of iNOS and Nox in vascular smooth muscle and demonstrating the functional consequences of iNOS and Nox during vascular injury. We describe the relevant literature demonstrating that the mitogen activated protein kinases (MAP kinases) are important modulators of pro-inflammatory cytokinedependent expression of iNOS. A central hypothesis discussed is that ROS-dependent regulation of the serine/threonine kinase protein kinase Cδ (PKCδ) is essential to understanding how Nox may regulate signaling pathways leading to iNOS expression. Overall, the integration of non-phagocytic NADPHoxidase with cytokine signaling in general and in vascular smooth muscle in particular is poorly understood and merit further investigation.

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[14] Modifications of cysteine-rich regions in protein kinase C induced by oxidant tumor promoters and enzyme-specific inhibitors

Cited by 49 publications

References 28 publications

Intracellular Signaling Pathways Involved in the Cell Growth Inhibition of Glioma Cells by Melatonin

Intracellular Signaling Pathways Involved in the Cell Growth Inhibition of Glioma Cells by Melatonin

Involvement of protein kinase C in crystalline silica-induced activation of the MAP kinase and AP-1 pathway

Regulation of smooth muscle by inducible nitric oxide synthase and NADPH oxidase in vascular proliferative diseases

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