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)

We have established an RNase protection method to quantify the expression of mRNA for the human protein kinase C (PK-C) isoforms alpha, beta 1, beta 2, and gamma. This was used to investigate whether each isoform is differentially expressed during the differentiation of hematopoietic cells. Myeloid and lymphoid cells express PK-C alpha, beta 1, and beta 2 mRNAs in various proportions. PK-C gamma mRNA was detected in human brain, but not in hematopoietic cells. PK-C alpha mRNA decreases as HL-60 cells mature to a neutrophil phenotype in response to retinoic acid, but its abundance does not change during monocytic differentiation in response to vitamin D3. PK-C alpha mRNA and protein were undetectable in peripheral blood neutrophils, but are present in monocytes. The mRNAs for PK-C beta 1 and beta 2 isoforms increase during HL-60 differentiation and are expressed in both neutrophils and monocytes. Therefore, the PK-C alpha isoform is specifically down-regulated during human neutrophil terminal differentiation. These data suggest that mature neutrophil functions do not require the PK-C alpha isoform.
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PMID:Down-regulation of human protein kinase C alpha is associated with terminal neutrophil differentiation. 161 Oct 98

Immune interactions in the heart were studied using a murine model of myosin-induced autoimmune myocarditis. A T cell hybridoma specific for mouse cardiac myosin was generated from A/J mice and used to demonstrate that endogenous myosin/I-Ak complexes are constitutively expressed on antigen-presenting cells in the heart. This T cell hybridoma, Seu.5, was used as a functional probe to identify a myocarditis-inducing epitope of cardiac myosin. Overlapping peptides based on the cardiac myosin heavy chain alpha (myhc alpha) sequences were synthesized and tested for their ability to stimulate Seu.5 T cells. One peptide, myhc alpha (325-357) strongly stimulated the Seu.5 T cells, localizing the epitope to this region of the myhc alpha molecule. Using truncated peptides, the epitope was further localized to residues 334-352. The myhc alpha (334-352) peptide strongly induced myocarditis when administered to A/J mice, which was histologically indistinguishable from that induced by myosin. The myhc alpha (334-352) epitope was present in cardiac myosin and not skeletal muscle myosins, providing a biochemical basis for the cardiac specificity of this autoimmune disease. Induction of myocarditis by this epitope was restricted to the myhc alpha isoform and not the myhc beta isoform, suggesting there may be a difference in the efficiency of generating tolerance to these isoforms of cardiac myosin, which are differentially developmentally regulated. The myhc alpha (334-352) epitope bound to purified I-Ak molecules in a similar manner to other I-Ak-restricted immunogenic epitopes, HEL(48-61) and RNase(43-56). Importantly, the myhc alpha (334-352) epitope was able to bind to I-Ak molecules on the surface of antigen-presenting cells in a stable manner. These findings demonstrate that autoantigenic epitopes can behave in a dominant manner and constitutively bind to class II molecules in the target organ in a similar manner to foreign immunogenic epitopes.
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PMID:Myocarditis-inducing epitope of myosin binds constitutively and stably to I-Ak on antigen-presenting cells in the heart. 759

Many neurotransmitters are known to regulate neuronal cell function by means of activation of cAMP-dependent protein kinase (PKA) and phosphorylation of neuronal substrate proteins, including transcription factors and ion channels. Here, we have characterized the gene expression of two isoforms of a protein kinase inhibitor (PKI) specific for PKA in mouse brain by RNase protection and in situ hybridization histochemistry. The studies demonstrate that the PKI alpha isoform is abundant in many regions of the adult mouse brain but particularly in cerebellum, hypothalamus, hippocampus, and cortex. In contrast, PKI beta is present at much lower levels in most brain regions but is found in significant amounts in the cerebellum, as well as in distinct nuclei within the pons, medulla, and hypothalamus. These results are consistent with a regulatory role of endogenous PKI in PKA-mediated signal transduction in brain and suggest differential functions for the two isoforms of PKI within the central nervous system.
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PMID:Differential expression of mRNAs for protein kinase inhibitor isoforms in mouse brain. 787 50

To characterize the expression of genes encoding the alpha- and beta-subunit isoforms of the Na(+)-K(+)-ATPase in rat kidney, we used reverse transcription (RT)-PCR of microdissected renal structures combined with quantitation of subunit isoform mRNAs in the major renal parenchymal zones. Transcripts for alpha 1, alpha 2, alpha 3, beta 1, and beta 2 subunit isoforms were detected by RT-PCR in microdissected glomeruli, proximal convoluted tubules, medullary thick ascending limbs of Henle, cortical and inner medullary collecting ducts. The truncated alpha 1 (alpha 1-T) isoform was also amplified from cortex, outer and inner medulla and isolated glomeruli, but it was not detected in these nephron segments. The DNA sequence of the renal alpha 1-T PCR product was identical to that of the cDNA previously cloned from aortic smooth muscle cells. RNA dot-blot analysis indicated that the alpha 1, alpha 2, and alpha 3 isoforms contributed approximately 70%, approximately 20%, and approximately 10%, respectively, of the total alpha isoform mRNA in each parenchymal zone. RNase protection assays determined that the beta 1 and beta 2 isoforms accounted for approximately 95% and approximately 5%, respectively, of the beta isoform mRNA in each zone. These data provide definitive evidence for the differential expression of mRNAs encoding all the alpha and beta isoforms in the renal parenchyma, and for the coexpression of these isoforms in the nephron segments examined. The results suggest the potential expression of up to eight different Na(+)-K(+)-ATPase isoenzymes in the kidney, and for multiple molecular levels of regulation of renal Na(+)-K(+)-ATPase expression.
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PMID:Segmental localization of mRNAs encoding Na(+)-K(+)-ATPase alpha- and beta-subunit isoforms in rat kidney using RT-PCR. 799 86

The aim of this study was to assess whether one of the most common poisons of cellular respiration, i.e., carbon dioxide, is proinflammatory. CO(2) is naturally present in the atmosphere at the level of 0.038% and involved in numerous cellular biochemical reactions. We analyzed in vitro the inflammation response induced by exposure to CO(2) for 48 h (0-20% with a constant O(2) concentration of 21%). In vivo mice were submitted to increasing concentrations of CO(2) (0, 5, 10, and 15% with a constant O(2) concentration of 21%) for 1 h. The exposure to concentrations above 5% of CO(2) resulted in the increased transcription (RNase protection assay) and secretion (ELISA) of proinflammatory cytokines [macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, MIP-2, IL-8, IL-6, monocyte chemoattractant protein-1, and regulated upon activation, normal T cell expressed, and, presumably, secreted (RANTES)] by epithelial cell lines HT-29 or A549 and primary pulmonary cells retrieved from the exposed mice. Lung inflammation was also demonstrated in vivo by mucin 5AC-enhanced production and airway hyperreactivity induction. This response was mostly mediated by the nuclear translocation of p65 NF-kappaB, itself a consequence of protein phosphatase 2A (PP2A) activation. Short inhibiting RNAs (siRNAs) targeted toward PP2Ac reversed the effect of carbon dioxide, i.e., disrupted the NF-kappaB activation and the proinflammatory cytokine secretion. In conclusion, this study strongly suggests that exposure to carbon dioxide may be more toxic than previously thought. This may be relevant for carcinogenic effects of combustion products.
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PMID:Carbon dioxide inhalation causes pulmonary inflammation. 1913 78