Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P67775 (alpha isoform)
 797 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein kinase C (PKC) is a family of enzymes involved in synapse formation and signal transduction at the neuromuscular junction. Two PKC isoforms, classical PKC alpha and novel PKC theta, have been shown to be enriched in skeletal muscle or localized to the endplate. We examined the role of nerve in regulating the expression of these PKC isoforms in rat skeletal muscle by denervating diaphragm muscle and measuring PKC protein expression at various postoperative times. nPKC theta protein levels decreased 65% after denervation, whereas cPKC alpha levels increased 80% compared with control hemidiaphragms. These results suggest that innervation regulates PKC theta and alpha isoform expression in skeletal muscle. To explore further how nerve regulates PKC expression, we characterized PKC isoform expression in rat myotubes deprived of neural input. Myoblast expression of nPKC theta was low, and the increase in nPKC theta expression that occurred during differentiation into myotubes resulted in levels of nPKC theta significantly below adult skeletal muscle. cPKC alpha expression in myoblastic increased during differentiation to levels that exceeded expression in adult skeletal muscle. Coculturing myotubes within neuroblastoma X glioma hybrid clonal cell line (NG108-15) increased nPKC theta expression, but not cPKC alpha, suggesting that nPKC theta in skeletal muscle and myotubes is regulated by nerve contact or by a factor(s) provided by nerve. Treating myotubes with tetrodotoxin did not affect either basal- or NG108-15 cell-stimulated nPKC theta expression. Together these results suggest that expression of nPKC theta in skeletal muscle is regulated by a transynaptic interaction with nerve that specifically influences nPKC theta expression.
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PMID:Neural influence on protein kinase C isoform expression in skeletal muscle. 875 30

Acquisition of resistance to anticancer agents is a serious problem for cancer chemotherapy. The present study analyzed the relationship between expression of the alpha isoform of deoxyribonucleic acid (DNA) topoisomerase II (topo II alpha) and chemosensitivity to topo II inhibitors by modulating the level of topo II alpha expression. A phosphorothioate analogue of an 18-nucleotide oligomer which is complementary to the translation initiation site of the human topo II alpha messenger ribonucleic acid sequence was used to suppress the expression of topo II alpha in a human glioma cell line (U373MG). The topo II alpha activity of the treated cells was reduced to 1/3 of untreated cells in a decatenation assay using kinetoplast DNA. Antisense oligoDNA-treated cells showed mild resistance to the topo II inhibitors, etoposide and adriamycin, of about 2.0 fold and 1.5 fold, respectively, compared to control cells. Only partial reduction in the activity of topo II alpha in the glioma cell line can cause a measurable resistance to topo II inhibitors, implying that the degree of topo II expression is correlated with chemosensitivity to topo II inhibitors.
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PMID:Induction of resistance to etoposide and adriamycin in a human glioma cell line treated with antisense oligodeoxynucleotide complementary to the messenger ribonucleic acid of deoxyribonucleic acid topoisomerase II alpha. 933 May 28

Intracellular signal transduction by the protein kinase C (PKC) family of enzymes plays a critical role in carcinogenesis and cellular growth regulation. Recent studies have suggested that the PKC isoform alpha may be a critical target for antiglioma therapy in humans (G. H. Baltuch et al., Can. J. Neurol. Sci., 22: 264-271, 1995). We studied the expression and subcellular distribution of the PKC alpha isoform in human high- and low-grade gliomas and also in glioma-derived cell lines with immunoblot analyses. Cell lines derived from high-grade gliomas expressed higher levels of PKC alpha than did cell lines derived from low-grade gliomas. In glioblastoma-derived cell lines, PKC alpha was mainly expressed in the soluble (cytosolic) fraction, indicating an inactive state of the enzyme. When analyzed in freshly frozen samples from human gliomas, the expression of PKC alpha was at similar levels in high- and low-grade tumors and was also similar to the levels in normal brain tissue controls. The PKC partial antagonist bryostatin 1, currently undergoing Phase II testing in patients with malignant gliomas, was capable of specifically down-regulating PKC alpha in vitro in glioblastoma-derived cell lines. However, this was not associated with significant growth inhibition. We conclude that the observed overexpression of PKC alpha in glioblastoma-derived cell lines may be an artifact of in vitro growth. Furthermore, we conclude that expression of PKC alpha in glioma-derived cell lines is not essential for cellular growth in vitro because down-regulation of PKC alpha following treatment with bryostatin 1 was not associated with growth inhibition.
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PMID:Disparity in expression of protein kinase C alpha in human glioma versus glioma-derived primary cell lines: therapeutic implications. 967 58

The 5' flanking region of the alpha isoform of the rat Ca2+/calmodulin-dependent protein kinase II (alpha CaM kinase II) gene was isolated in 2.3 kbp of genomic sequence. Functional analysis of alpha CaM kinase II promoter deletion mutants fused to a reporter gene in neuroblastoma, including N18TG2, NG108-15, and CAD cells revealed strong transcriptional activity localized 100-145 bp, and a potent silencer 199-275 bp upstream of the transcription start site. The promoter is inactive in non-neuronal cells including BALB/c 3T3, Chinese hamster ovary, HT1080, and C6 glioma cells. These results indicated that the alpha CaM kinase II gene is transcribed from a tissue-specific promoter which is under intense negative control.
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PMID:Characterization of 5' flanking region of alpha isoform of rat Ca2+/calmodulin-dependent protein kinase II gene and neuronal cell type specific promoter activity. 1142 14

Radiotherapy is the primary and most important adjuvant therapy for malignant gliomas. Although the mechanism of radiation resistance in gliomas has been studied for decades, it is still not clear how the resistance is related with functions of molecular chaperones in the endoplasmic reticulum. Calreticulin (CRT) is a Ca(2+)-binding molecular chaperone in the endoplasmic reticulum. Recently, it was reported that changes in intracellular Ca(2+) homeostasis play a role in the modulation of apoptosis. In the present study, we found that the level of CRT was higher in neuroglioma H4 cells than in glioblastoma cells (U251MG and T98G), and was well correlated with the sensitivity to gamma-irradiation. To examine the role of CRT in the radiosensitivity of malignant gliomas, the CRT gene was introduced into U251MG cells, which express low levels of CRT, and the effect of overexpression of CRT on the radiosensitivity was examined. The cells transfected with the CRT gene exhibited enhanced radiation-induced apoptosis compared with untransfected control cells. In CRT-overexpressing cells, cell survival signaling via Akt was markedly suppressed. Furthermore, the gene expression of protein phosphatase 2Ac alpha (PP2Ac alpha), which is responsible for the dephosphorylation and inactivation of Akt, was up-regulated in CRT-overexpressing cells, and the regulation was dependent on Ca(2+). Thus, overexpression of CRT modulates radiation-induced apoptosis by suppressing Akt signaling through the up-regulation of PP2Ac alpha expression via altered Ca(2+) homeostasis. These results show the novel mechanism by which CRT is involved in the regulation of radiosensitivity and radiation-induced apoptosis in malignant glioma cells.
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PMID:Calreticulin, a molecular chaperone in the endoplasmic reticulum, modulates radiosensitivity of human glioblastoma U251MG cells. 1695 Nov 81

PPP2R2C encodes a gamma isoform of the subunit B55 subfamily, which is a regulatory subunit of Protein phosphatase type 2A (PP2A). Our study shows that PPP2R2C is downregulated in glioma cells and human brain cancer patient samples. Overexpression of PPP2R2C inhibited cancer cell proliferation both in vitro and in vivo through the suppression of the activity of S6K in the mTOR pathway. Moreover, exogenous expression of PPP2R2C promoted the formation of a complex with the PP2A-C subunit to further enhance the binding of PP2A-C with S6K. Our results suggest that PPP2R2C is a potential tumor suppressor gene in human brain cancers. This study will provide novel insight into the development of therapeutic strategies in the treatment of human brain tumors.
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PMID:Over expression of PPP2R2C inhibits human glioma cells growth through the suppression of mTOR pathway. 2412 60