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Susan F. Steinberg - One of the best experts on this subject based on the ideXlab platform.
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Do adult rat ventricular myocytes express protein kinase C-Alpha?
American Journal of Physiology-Heart and Circulatory Physiology, 1997Co-Authors: Vitalyi O. Rybin, Susan F. SteinbergAbstract:Although calcium-insensitive protein kinase C (PKC) isoforms (PKC-epsilon and PKC-delta) are consistently detected in adult ventricular myocytes, the evidence that adult ventricular myocytes also express calcium-sensitive PKC-Alpha is inconsistent. The current study used four different anti-PKC-Alpha-antibodies to resolve some of the uncertainties regarding the immunodetection of PKC-Alpha in adult ventricular myocytes. Three of the antibodies used in this study barely (GIBCO-BRL) or rather faintly (Transduction Laboratories and Seikagaku America) recognize PKC-Alpha in crude preparations from adult ventricular myocytes. Although each of these antibodies recognizes a prominent 80-kDa band, which is similar in size to PKC-Alpha, this represents nonspecific immunoreactivity and should not be confused with PKC-Alpha. This conclusion is based on peptide-blocking experiments (GIBCO-BRL), the absence of the requisite sensitivity to calcium- and phorbol 12-myristate 13-acetate-induced translocation (Seikagaku America and Transduction Laboratories), and/or the failure to copurify with PKC-Alpha on DEAE-Sephacel chromatography. Nevertheless, an antibody from Upstate Biotechnology clearly recognizes PKC-Alpha and not other unrelated nonspecific immunoreactive species in crude preparations from adult ventricular myocytes. Each of the antisera used in this study could detect PKC-Alpha immunoreactivity following chromatographic purification of the samples to enrich for PKC-Alpha and remove nonspecific immunoreactive proteins. These results suggest that PKC-Alpha is expressed by adult ventricular myocytes and argue that differences in the sensitivity and/or specificity of available antisera contribute to at least some of the confusion regarding PKC-Alpha expression in adult ventricular myocytes.
Vitalyi O. Rybin - One of the best experts on this subject based on the ideXlab platform.
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Do adult rat ventricular myocytes express protein kinase C-Alpha?
American Journal of Physiology-Heart and Circulatory Physiology, 1997Co-Authors: Vitalyi O. Rybin, Susan F. SteinbergAbstract:Although calcium-insensitive protein kinase C (PKC) isoforms (PKC-epsilon and PKC-delta) are consistently detected in adult ventricular myocytes, the evidence that adult ventricular myocytes also express calcium-sensitive PKC-Alpha is inconsistent. The current study used four different anti-PKC-Alpha-antibodies to resolve some of the uncertainties regarding the immunodetection of PKC-Alpha in adult ventricular myocytes. Three of the antibodies used in this study barely (GIBCO-BRL) or rather faintly (Transduction Laboratories and Seikagaku America) recognize PKC-Alpha in crude preparations from adult ventricular myocytes. Although each of these antibodies recognizes a prominent 80-kDa band, which is similar in size to PKC-Alpha, this represents nonspecific immunoreactivity and should not be confused with PKC-Alpha. This conclusion is based on peptide-blocking experiments (GIBCO-BRL), the absence of the requisite sensitivity to calcium- and phorbol 12-myristate 13-acetate-induced translocation (Seikagaku America and Transduction Laboratories), and/or the failure to copurify with PKC-Alpha on DEAE-Sephacel chromatography. Nevertheless, an antibody from Upstate Biotechnology clearly recognizes PKC-Alpha and not other unrelated nonspecific immunoreactive species in crude preparations from adult ventricular myocytes. Each of the antisera used in this study could detect PKC-Alpha immunoreactivity following chromatographic purification of the samples to enrich for PKC-Alpha and remove nonspecific immunoreactive proteins. These results suggest that PKC-Alpha is expressed by adult ventricular myocytes and argue that differences in the sensitivity and/or specificity of available antisera contribute to at least some of the confusion regarding PKC-Alpha expression in adult ventricular myocytes.
Kathleen G Morgan - One of the best experts on this subject based on the ideXlab platform.
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inhibition of PKC Alpha and rhoa translocation in differentiated smooth muscle by a caveolin scaffolding domain peptide
Experimental Cell Research, 2000Co-Authors: Michael J Taggart, Paul C Leavis, Olivier Feron, Kathleen G MorganAbstract:Receptor-coupled contraction of smooth muscle involves recruitment to the plasma membrane of downstream effector molecules PKC Alpha and rhoA but the mechanism of this signal integration is unclear. Caveolins, the principal structural proteins of caveolar plasma membrane invaginations, have been implicated in the organization and regulation of many signal transducing molecules. Thus, using laser scanning confocal immunofluorescent microscopy, we tested the hypothesis that caveolin is involved in smooth muscle signaling by investigating caveolin isoform expression and localization, together with the effect of a peptide inhibitor of caveolin function, in intact differentiated smooth muscle cells. All three main caveolin isoforms were identified in uterine, stomach, and ileal smooth muscles and assumed a predominantly plasma membranous localization in myometrial cells. Cytoplasmic introduction of a peptide corresponding to the caveolin-1 scaffolding domain-an essential region for caveolin interaction with signaling molecules-significantly inhibited agonist-induced translocation of both PKC Alpha and rhoA. Translocation was unimpaired by a scrambled peptide and was unaltered in sham-treated cells. The membranous localization of caveolins, and direct inhibition of receptor-coupled PKC Alpha and rhoA translocation by the caveolin-1 scaffolding domain, supports the concept that caveolins can regulate the integration of extracellular contractile stimuli and downstream intracellular effecters in smooth muscle. (C) 2000 Academic Press.
Karen Sundell - One of the best experts on this subject based on the ideXlab platform.
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Protein Kinase C Alpha Expression in Breast and Ovarian Cancer
Oncology, 2004Co-Authors: Michael Lahn, Karen Sundell, Gabriele Köhler, Blake M. Paterson, Thomas Frank BumolAbstract:In recent years research has focused on the development of specific, targeted drugs to treat cancer. One approach has been to block intracellular signaling proteins, such as protein kinase C Alpha (PKC-Alpha). To help support the rationale for clinical studies of a PKC-Alpha-targeted therapy in breast and ovarian cancers, we reviewed publications studying PKC-Alpha expression in these tumors. Since these investigations were mostly performed in cell lines, we supplemented this review with some preliminary findings from studies examining PKC-Alpha expression in tumor tissue biopsies obtained from patients with breast and ovarian cancer. Based on the reviewed publications using representative cell lines and our preliminary findings on tumor tissue of patients with breast cancer, we infer that PKC-Alpha levels may especially be increased in breast cancer patients with low or negative estrogen receptor (ER) levels. Thus, clinical studies determining efficacy of selective or specific inhibitors of PKC-Alpha should include determination of ER status in order to help answer whether blocking PKC-Alpha in patients with low or absent ER can result in clinical benefit.
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The role of protein kinase C-Alpha (PKC-Alpha) in melanoma.
Melanoma research, 2004Co-Authors: Michael Lahn, Karen SundellAbstract:In the 1980s, protein kinase C (PKC) was identified as a contributing factor in skin tumorigenesis. As drugs targeting specifically PKC have become available, the intent of this review was to assess the role of PKC, in particular of PKC-Alpha in melanoma or other skin cancers. We reviewed and summarized published studies examining the role of PKC-Alpha in the development of melanoma or other skin cancers. Most studies to date have been cell-culture based. In models of melanoma, PKC-Alpha activation is typically associated with increased tumour cell proliferation, invasiveness and decreased differentiation, suggesting that PKC-Alpha inhibitors, such as aprinocarsen, an antisense oligonucleotide directed against PKC-Alpha, may be appropriate in the treatment of skin malignancies. Because of the recent developments on selective or specific PKC-Alpha inhibitors, including aprinocarsen, there is a growing need to conduct further translational research, especially in melanoma patients, to identify the patient population that might benefit most from PKC-Alpha targeted therapy.
Allen M. Samarel - One of the best experts on this subject based on the ideXlab platform.
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Protein kinase C-Alpha-induced hypertrophy of neonatal rat ventricular myocytes.
American journal of physiology. Heart and circulatory physiology, 2004Co-Authors: Kalpana Vijayan, Erika L Szotek, Jody L. Martin, Allen M. SamarelAbstract:Protein kinase C (PKC) isoenzymes play a critical role in cardiomyocyte hypertrophy. At least three different phorbol ester-sensitive PKC isoenzymes are expressed in neonatal rat ventricular myocytes (NRVMs): PKC-Alpha, -delta, and -epsilon. Using replication-defective adenoviruses (AdVs) that express wild-type (WT) and dominant-negative (DN) PKC-Alpha together with phorbol myristate acetate (PMA), which is a hypertrophic agonist and activator of all three PKC isoenzymes, we studied the role of PKC-Alpha in signaling-specific aspects of the hypertrophic phenotype. PMA induced nuclear translocation of endogenous and AdV-WT PKC-Alpha in NRVMs. WT PKC-Alpha overexpression increased protein synthesis and the protein-to-DNA (P/D) ratio but did not affect cell surface area (CSA) or cell shape compared with uninfected or control AdV beta-galactosidase (AdV betagal)-infected cells. PMA-treated uninfected cells displayed increased protein synthesis, P/D ratio, and CSA and elongated morphology. PMA did not further enhance protein synthesis or P/D ratio in AdV-WT PKC-Alpha-infected cells. To assess the requirement of PKC-Alpha for these PMA-induced changes, AdV-DN PKC-Alpha or AdV betagal-infected NRVMs were stimulated with PMA. Without PMA, AdV-DN PKC-Alpha had no effects on protein synthesis, P/D ratio, CSA, or shape vs. AdV betagal-infected NRVMs. PMA increased protein synthesis, P/D ratio, and CSA in AdV betagal-infected cells, but these parameters were significantly reduced in PMA-stimulated AdV-DN PKC-Alpha-infected NRVMs. Overexpression of DN PKC-Alpha enhanced PMA-induced cell elongation. Neither WT PKC-Alpha nor DN PKC-Alpha affected atrial natriuretic factor gene expression. Insulin-like growth factor-1 also induced nuclear translocation of endogenous PKC-Alpha. PMA but not WT PKC-Alpha overexpression induced ERK1/2 activation. However, AdV-DN PKC-Alpha partially blocked PMA-induced ERK activation. Thus PKC-Alpha is necessary for certain aspects of PMA-induced NRVM hypertrophy.