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Results for “Protein Isoforms”

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PubMed1994

Differential expression of synaptic vesicle protein 2 (SV2) isoforms.

The synaptic vesicle proteins SV2A and SV2B (SV2 = synaptic vesicle protein 2) are two highly related proteins belonging to a family of transporters. As a first step toward identifying the function of the SV2 proteins, we examined the expression of SV2A and SV2B in the rat brain by in situ hybridization, immunohistochemistry, and immunoprecipitation with isoform-specific antibodies. These analyses revealed that one isoform, SV2A, is expressed ubiquitously throughout the brain at varying levels. The other isoform, SV2B, has a more limited distribution with varying degrees of coexpression with SV2A. Immunoprecipitation of brain synaptic vesicles with isoform-specific antibodies followed by Western analyses suggests that both isoforms can be present on the same synaptic vesicle. The expression of the SV2 proteins did not correlate either with neurotransmitter phenotype or with the expression of other synaptic vesicle protein isoforms. SV2B expression was observed to change during development; it is more widely expressed in the immature brain and is found in cells that have yet to establish synaptic contacts. The ubiquitous and overlapping expression of the SV2s suggests that they perform a function common to all synaptic vesicles. Variable and changing coexpression of the SV2 isoforms may indicate that SV2 function is regulated by the isoform composition of synaptic vesicles. The observation that the synaptic vesicle proteins, all occurring in multiple isoforms, are differentially expressed with respect to each other indicates that up to 90 different vesicle types are possible.

Animals↗

PubMed2004

Alternative splicing of the APC gene in the neural retina and retinal pigment epithelium.

PURPOSE: Hypertrophy and hyperplasia of the retinal pigment epithelium (RPE) is associated with an inherited predisposition to human familial adenomatous polyposis coli, suggesting that expression of the adenomatous polyposis coli (APC) tumor suppressor may regulate RPE proliferation/differentiation. Distinctive APC isoforms exist in different cell types due to alternative splicing of the APC transcripts. We hypothesize that differences in expression patterns of APC protein isoforms are critical to RPE proliferation/differentiation. METHODS: To investigate these relationships, APC gene expression was characterized in the retinas and RPE from fetal and adult human and mouse, and in the epiretinal membranes (ERM) from 5 patients with proliferative vitreoretinopathy (PVR). Expression patterns of alternative splice-forms of APC transcripts were evaluated by comparative quantitative RT-PCR. Exon 1 of APC encodes a heptad repeat that confers the ability of APC to homodimerize. APC protein isoforms containing or lacking this heptad were characterized by western blot analysis and immunohistochemistry. RESULTS: Comparative quantitative RT-PCR demonstrated a predominant exon 1 containing, conventional APC splice-form in the early developing fetal RPE and retina, and in all the tested ERM samples from patients with PVR. This method also demonstrated an increased level of exon 1 lacking APC splice-form in the mature RPE and retina. Western blot analysis and immunofluorescence microscopy demonstrated the conventional APC only in the RPE, and the APC isoform without the first heptad repeat in both the retina and RPE. Immunofluorescence microscopy also demonstrated only the conventional APC in the ERM samples tested. CONCLUSIONS: These results suggest that alternative splicing of APC leads to differential APC expression with potentially unique functions. APC isoform without the first heptad repeat may play a role in cell cycle cessation in the adult retina and RPE, and the down regulation of this APC isoform may contribute to the potential of RPE to migrate and proliferate.

Adenomatous Polyposis Coli Protein↗

PubMed1996

The eta isoform of protein kinase C mediates transcriptional activation of the human transglutaminase 1 gene.

Transglutaminase 1 (TGase 1) is expressed during the terminal differentiation of keratinized squamous epithelium to form cornified cell envelope in differentiated keratinocytes by the epsilon-(gamma-glutamyl) cross-linking reaction. The gene for human TGase 1 is responsible for autosomal recessive lamellar ichthyosis, a severe hereditary keratinizing disorder of the skin. We examined the transcriptional activity of the gene in FRSK, rat keratinocytic cells, transfected with the luciferase reporter gene under control of the 5' upstream region of human TGase 1 gene. Transfection of the reporter gene with an expression vector for the eta isoform of novel protein kinase C (nPKCeta), as well as exposure to 12-0-tetradecanoylphorbol-13-acetate, markedly increased the luciferase activity in FRSK, but not in HT-1080 fibrosarcoma cells, although exogenous nPKCeta was expressed in both. The induction was suppressed by deleting the TGase 1 upstream sequence from -95 to -67 and by deleting the kinase domain from exogenous nPKCeta. In comparison with other PKC isoforms, nPKCeta most effectively induced the luciferase activity. We suggest that nPKCeta, an epithelium-specific isoform of PKC, mediates the activation of the TGase 1 transcription.

Animals↗

PubMed2000

Molecular cloning of a novel human I-mfa domain-containing protein that differently regulates human T-cell leukemia virus type I and HIV-1 expression.

Regulation of viral genome expression is the result of complex cooperation between viral proteins and host cell factors. We report here the characterization of a novel cellular factor sharing homology with the specific cysteine-rich C-terminal domain of the basic helix-loop-helix repressor protein I-mfa. The synthesis of this new factor, called HIC for Human I-mfa domain-Containing protein, is controlled at the translational level by two different codons, an ATG and an upstream non-ATG translational initiator, allowing the production of two protein isoforms, p32 and p40, respectively. We show that the HIC protein isoforms present different subcellular localizations, p32 being mainly distributed throughout the cytoplasm, whereas p40 is targeted to the nucleolus. Moreover, in trying to understand the function of HIC, we have found that both isoforms stimulate in T-cells the expression of a luciferase reporter gene driven by the human T-cell leukemia virus type I-long terminal repeat in the presence of the viral transactivator Tax. We demonstrate by mutagenesis that the I-mfa-like domain of HIC is involved in this regulation. Finally, we also show that HIC is able to down-regulate the luciferase expression from the human immunodeficiency virus type 1-long terminal repeat induced by the viral transactivator Tat. From these results, we propose that HIC and I-mfa represent two members of a new family of proteins regulating gene expression and characterized by a particular cysteine-rich C-terminal domain.

Amino Acid Sequence↗

PubMed2006

Effects of postnatal steroids on Na+/K+-ATPase activity and alpha1- and beta1-subunit protein expression in the cerebral cortex and renal cortex of newborn lambs.

Na(+)/K(+)-ATPase is a membrane-bound enzyme responsible for Na(+)/K(+) translocation across cell membranes. It is essential for the generation of electrochemical gradients, which control the ionic environment necessary for electrical activity and water and electrolyte balance. Newborn infants who are at risk of developing bronchopulmonary dysplasia (BPD) are frequently treated with corticosteroids. Although these infants are at risk for neurological, water and electrolyte abnormalities, there is little information regarding the effects of clinically relevant doses of corticosteroids on Na(+)/K(+)-ATPase activity and protein isoform expression in the brain and kidney of newborns. In the present study, we examined the effects of dexamethasone on cerebral cortical and renal cortical Na(+)/K(+)-ATPase activity and alpha1- and beta1-protein isoform expression in newborn lambs. Lambs were given four injections of a placebo (n = 11) or one of three different doses of dexamethasone (0.01 mg kg(-1), n = 9; 0.25 mg kg(-1), n = 11; or 0.50 mg kg(-1), n = 9) 12 h apart on Postnatal Days 3 and 4 up to 18 h before harvest of the cerebral cortex and renal cortex. We selected doses in a range to approximate those used to treat infants with BPD. Na(+)/K(+)-ATPase activity was measured in membrane preparations as ouabain-sensitive inorganic phosphate liberation from ATP and alpha1- and beta1-subunit abundance by Western immunoblot. Postnatal treatment of lambs with dexamethasone resulted in a 21.4% increase in Na(+)/K(+)-ATPase activity and a 30.4% increase in catalytic alpha1-protein expression in the cerebral cortex at a dose of 0.50 mg kg(-1) dexamethasone, but not at the lower doses. Dexamethasone treatment was not associated with changes in beta1-isoform expression in the cerebral cortex. In the kidney, dexamethasone treatment was not associated with significant changes in Na(+)/K(+)-ATPase activity or alpha1- or beta1-isoform expression for the doses we examined. Therefore, clinically relevant corticosteroid treatment exerts dose-related, differential organ-specific effects on Na(+)/K(+)-ATPase activity and protein isoform expression in newborn lambs.

Adenosine Triphosphate↗

PubMed1996

Changes in expression of lymphocyte amyloid precursor protein mRNA isoforms in normal aging and Alzheimer's disease.

We measured, by employing a quantitative reverse-transcriptase PCR procedure, the relative (to beta-actin) levels of amyloid precursor protein APP751 and APP770 mRNA isoforms in lymphocytes obtained from 64 cognitively intact subjects ranging in ages from 20 to 91 years and in 19 patients with sporadic Alzheimer's disease. A positive correlation was observed between the relative lymphocyte APP751 mRNA levels and subject age for the cognitively intact cohort. No difference in lymphocyte APP751 mRNA levels was observed between Alzheimer's disease patients and their age-matched controls (> 55 years of age). However, the ratio of lymphocyte APP751:APP770 mRNA levels was significantly lower in Alzheimer's disease subjects compared to the > 55-year-old cohort. This decreased ratio is most likely due to an average 31% increase in the lymphocyte APP770 isoform in Alzheimer's disease patients compared to 12% in the > 55-year-old cognitively intact group. Marked individual differences in amount of APP mRNA isoforms were encountered among all the subject groups and in the < or = 55-year-old cohort, a 10-fold variation in individual APP751 mRNA levels was observed. The relevance of these findings in lymphocytes to the pathogenesis of Alzheimer's disease is discussed.

Actins↗

PubMed1999

Protein kinase C isoforms in the epidermal tissues of normal and postburn human skin.

Because the expression of the isoforms of protein kinase C (PKC) in human basal keratinocytes is not understood, the expression of PKC isoforms were screened in specimens of epidermal tissue from postburn skin and the normal locations for skin grafts in patients with second or higher degrees of flame injury. The expression of individual isoform was determined by Western blot technique. Only PKC alpha and zeta were detected in the epidermal tissues of normal and postburn skin and translocation occurred in PKC alpha. Patients without antibiotic treatment after flame injury had higher expressions of PKC alpha and zeta. These findings indicate that the mechanisms of cellular differentiation and growth in postburn epidermal tissue may be related to the expression and translocation of PKC alpha induced by intra- and extracellular stimulation. These changes in PKC alpha further activate the DAG/PKC signal transduction pathways.

Adult↗

PubMed2002

Role for G protein Gbetagamma isoform specificity in synaptic signal processing: a computational study.

Computational modeling is used to investigate the functional impact of G protein-mediated presynaptic autoinhibition on synaptic filtering properties. It is demonstrated that this form of autoinhibition, which is relieved by depolarization, acts as a high-pass filter. This contrasts with vesicle depletion, which acts as a low-pass filter. Model parameters are adjusted to reproduce kinetic slowing data from different Gbetagamma dimeric isoforms, which produce different degrees of slowing. With these sets of parameter values, we demonstrate that the range of frequencies filtered out by the autoinhibition varies greatly depending on the Gbetagamma isoform activated by the autoreceptors. It is shown that G protein autoinhibition can enhance the spatial contrast between a spatially distributed high-frequency signal and surrounding low-frequency noise, providing an alternate mechanism to lateral inhibition. It is also shown that autoinhibition can increase the fidelity of coincidence detection by increasing the signal-to-noise ratio in the postsynaptic cell. The filter cut, the input frequency below which signals are filtered, depends on several biophysical parameters in addition to those related to Gbetagamma binding and unbinding. By varying one such parameter, the rate at which transmitter unbinds from autoreceptors, we show that the filter cut can be adjusted up or down for several of the Gbetagamma isoforms. This allows for great synapse-to-synapse variability in the distinction between signal and noise.

Artifacts↗

PubMed2003

Polymorphisms in the SEEK1 and SPR1 genes on 6p21.3 associate with psoriasis in the Swedish population.

Psoriasis is a chronic skin disease that results in red and scaly lesions. Several psoriasis susceptibility loci have been identified across the genome, of which PSORS1 on 6p21.3 is predominant. There is an ongoing debate regarding whether the HLA-C allele, Cw*0602, can be considered the major predisposing factor in this region. Investigation of other genes in the PSORS1 region with regard to psoriasis may provide alternate candidates to HLA-C. We have characterized two overlapping genes, SEEK1 and SPR1. SEEK1 encodes two putative protein isoforms: the first being one of 152 amino acids from the full-length splice-isoform (exon 1-6), and the second being one of 100 amino acids from an alternate splice-isoform (exon 1 and 6). SPR1 encodes a highly conserved protein of 134 amino acids, and in addition to characterization of human SPR1 we report the cloning of its orthologs in mouse and pig. Both SEEK1 and SPR1 are expressed in normal and psoriasis skin. In a case-control study, five of the nine single nucleotide polymorphisms (SNPs) found in SEEK1 were associated with psoriasis, while one of the four SNPs found in SPR1 showed association. Testing the Cw*0602 confounding status revealed that two of the SEEK1 SNPs showed Cw*0602-independent association, while the SPR1 SNP showed Cw*0602-dependent association. The second exon of SEEK1, containing the two Cw*0602-independent SNPs, showed the highest concentration of the psoriasis-associating SNPs, but did not appear to be translated.

Adolescent↗

PubMed2006

Coiled-coil interactions modulate multimerization, mitochondrial binding and kinase activity of myotonic dystrophy protein kinase splice isoforms.

The myotonic dystrophy protein kinase polypeptide repertoire in mice and humans consists of six different splice isoforms that vary in the nature of their C-terminal tails and in the presence or absence of an internal Val-Ser-Gly-Gly-Gly motif. Here, we demonstrate that myotonic dystrophy protein kinase isoforms exist in high-molecular-weight complexes controlled by homo- and heteromultimerization. This multimerization is mediated by coiled-coil interactions in the tail-proximal domain and occurs independently of alternatively spliced protein segments or myotonic dystrophy protein kinase activity. Complex formation was impaired in myotonic dystrophy protein kinase mutants in which three leucines at positions a and d in the coiled-coil heptad repeats were mutated to glycines. These coiled-coil mutants were still capable of autophosphorylation and transphosphorylation of peptides, but the rates of their kinase activities were significantly lowered. Moreover, phosphorylation of the natural myotonic dystrophy protein kinase substrate, myosin phosphatase targeting subunit, was preserved, even though binding of the myotonic dystrophy protein kinase to the myosin phosphatase targeting subunit was strongly reduced. Furthermore, the association of myotonic dystrophy protein kinase isoform C to the mitochondrial outer membrane was weakened when the coiled-coil interaction was perturbed. Our findings indicate that the coiled-coil domain modulates myotonic dystrophy protein kinase multimerization, substrate binding, kinase activity and subcellular localization characteristics.

Amino Acid Sequence↗

PubMed1995

Differential expression levels of the heat shock protein 27 isoforms in pediatric normal, nonleukemic and common acute lymphoblastic leukemia B-cell precursors.

Heat shock protein 27 (hsp27) may function as a regulator of microfilament dynamics and may participate in signal transduction pathways of different cell growth regulators, with the mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 being a major enzyme responsible for its phosphorylation. Using two-dimensional gel electrophoresis, we have compared the expression levels of two hsp27 isoelectric variants (hsp27 isoforms) M2 (molecular weight, 26 kD; isoelectric point, 6.02) and M3 (molecular weight, 26 kD; isoelectric point, 5.60) in pediatric bone marrow CD19+CD10+B-cell precursors (BCPs) purified from either common acute lymphoblastic leukemia (c-ALL) patients, normal donors, or non-c-ALL patients. Compared with normal BCPs, we found increased hsp27 expressions (M2 isoform) (by a factor 5 to 9 of mean level) in c-ALL as well as in non-c-ALL (nonleukemic) precursors. Though increased phosphorylation of hsp27 (M3 isoform) was observed in BCPs from c-ALL patients at relapse (by a factor 3 of mean level compared with normal BCPs and precursors from c-ALL at diagnosis), which might represent a differential enzymatic activity, this was not distinguishable from that of non-c-ALL patients. Therefore, our studies suggest constitutive differences of hsp27 isoforms between pediatric leukemic BCPs and their relatively low-expressing, immunophenotypically normal bone marrow counterparts. In light of the occasional and possibly transient increase of hsp27 expression during nonleukemic BCP differentiation and the possible role of hsp27 in signal transduction to microfilaments, these differences might be of considerable biologic interest and of importance in future studies of regulated normal or dysregulated leukemic hematopoietic cellular differentiation.

Adolescent↗

PubMed1999

Rice calcium-dependent protein kinase isoforms OsCDPK2 and OsCDPK11 show different responses to light and different expression patterns during seed development.

We investigated the spatial and temporal expression patterns of two rice calcium-dependent protein kinases (CDPKs), OsCDPK2 and OSCDPK11, using isoform-specific antisera. Bands of the expected molecular sizes for OsCDPK2 (59 kDa) and OsCDPK11 (61 kDa) were detected on western blots. OsCDPK2 and OsCDPK11 mRNA and protein levels increased in unison during flower development. However, at the onset of seed development, the protein expression profiles diverged significantly. OsCDPK2 protein was expressed at low levels during early seed development, but increased to high levels that were maintained in later stages (20 days after fertilisation, DAF). Conversely, OsCDPK11 protein levels were high at the beginning of seed development, but fell rapidly from 10 DAF onwards. This decrease in the level of OsCDPK11 protein was associated with the abundant synthesis of a truncated mRNA species. OsCDPK2 expression was also closely associated with light perception. OsCDPK2 protein was barely detectable in green leaves exposed to light, but levels increased sharply when plants were shifted to darkness. Initially, this increase reflected a rapid elevation in the levels of OsCDPK2 mRNA, which was normally located in the mesophyll. Conversely, OsCDPK11 mRNA and protein levels were unaffected by light. These data strongly indicate that two rice CDPK isoforms have different functions in seed development and in response to light in leaves.

Blotting, Western↗

PubMed2002

Apolipoprotein E isoform mediated regulation of nitric oxide release.

Progressive dysfunction and death of neurons in Alzheimer's dementia is enhanced in patients carrying one or more APOE4 alleles who also display increased presence of oxidative stress markers. Modulation of oxidative stress is a nontraditional and physiologically relevant immunomodulatory function of apolipoprotein E (apoE). Stimulated peritoneal macrophages from APOE-transgenic replacement (APOE-TR) mice expressing only human apoE3 or human apoE4 protein isoforms were utilized as mouse models to investigate the role of apoE protein isoforms and gender in the regulation of oxidative stress. Macrophages from male APOE4/4-TR mice produced significantly higher levels of nitric oxide than from male APOE3/3-TR mice, while macrophages from female APOE3/3-TR and female APOE4/4-TR mice produced the similar levels of nitric oxide. Primary cultures of microglial cells of APOE4 transgenic mice also produced significantly more nitric oxide than microglia from APOE3 transgenic mice. These data suggest a potentially novel mechanism for gender-dependent and apoE isoform-dependent immune responses that parallel the genetic susceptibility of APOE4 carriers for the development of Alzheimer's disease.

Alzheimer Disease↗

PubMed2000

Cloning and characterization of two overlapping genes in a subregion at 6q21 involved in replicative senescence and schizophrenia.

Two new genes were cloned from region 6q21 and characterized. One gene, C6orf4-6, expresses three mRNA isoforms diverging at the 5' and 3' ends, and encodes two protein isoforms that differ by nine amino acids at their amino terminus. The second gene, C6UAS, is transcribed in the antisense orientation from the complementary strand of C6orf4-6. C6UAS overlaps the second exon of C6orf4, where the start codon of protein isoform 1 is located. C6UAS has no apparent ORF and most likely represents a structural RNA gene that is transcribed but not translated. This feature and the antisense polarity of transcription suggest that C6UAS could play a regulatory role on the expression of C6orf4, as indicated by a significant decrease of endogenous C6orf4 expression after transfection of C6UAS cDNA in human fibroblasts. Neither C6UAS nor C6orf4-6 genes show any homology with known human genes. The two genes were cloned from a subregion at 6q21 containing a replicative senescence gene, a tumor suppressor gene and a gene involved in hereditary schizophrenia. In addition, the common fragile site FRA6F was mapped in the same region. Cloning and characterization of C6orf4-6 and C6UAS may help to clarify the structure and the functional role of this important region.

Amino Acid Sequence↗

PubMed1997

Identification of protein kinase C isoforms in marine mussels.

In this paper we have examined the distribution of some isoforms of protein kinase C in different tissues from the sea mussel Mytilus galloprovincialis Lmk.. By immunoblot analysis, we have detected the presence of at least three PKC isoforms, all preferably associated with the cellular cytosolic fraction. The Ca(2+)-independent form PKC delta was separated from the Ca(2+)-dependent forms (PKC alpha and beta) by means of an ionic change chromatography on DE-52. A comparative study was carried out on the phosphorylatable non-artificial substrates. The M.B.P. protein proved to be the best substrate, while the worst was HIIIS histone which, however, is frequently used in evaluation assays of the activity.

Animals↗

PubMed2006

Characterization of endogenous human promyelocytic leukemia isoforms.

Promyelocytic leukemia (PML) has been implicated in a variety of functions, including control of TP53 function and modulation of cellular senescence. Sumolated PML is the organizer of mature PML bodies, recruiting a variety of proteins onto these nuclear domains. The PML gene is predicted to encode a variety of protein isoforms. Overexpression of only one of them, PML-IV, promotes senescence in human diploid fibroblasts, whereas PML-III was proposed to specifically interact with the centrosome. We show that all PML isoform proteins are expressed in cell lines or primary cells. Unexpectedly, we found that PML-III, PML-IV, and PML-V are quantitatively minor isoforms compared with PML-I/II and could not confirm the centrosomal targeting of PML-III. Stable expression of each isoform, in a pml-null background, yields distinct subcellular localization patterns, suggesting that, like in other RBCC/TRIM proteins, the COOH-terminal domains of PML are involved in interactions with specific cellular components. Only the isoform-specific sequences of PML-I and PML-V are highly conserved between man and mouse. That PML-I contains all conserved exons and is more abundantly expressed than PML-IV suggests that it is a critical contributor to PML function(s).

Animals↗

PubMed1989

Human ventricular/slow twitch myosin alkali light chain gene characterization, sequence, and chromosomal location.

The gene coding for the human ventricular/slow twitch myosin alkali light chain isoform was isolated and sequenced. It was found to contain a total of seven exons, the last of which is completely 3'-untranslated sequence. Comparison of this gene sequence with that of the various fast twitch skeletal isoform gene sequences revealed that the exon-intron arrangement is conserved within the myosin alkali light chain gene family. In fact the introns are in exactly the same positions within analogous codons. Comparison of the derived amino acid sequence from the human ventricular/slow twitch isoform gene with that of other isoform protein sequences indicated that the protein encoded by this gene is more homologous to the chicken cardiac isoform protein sequence than to any of the other protein sequences. These results indicate that the gene duplication which gave rise to the ventricular/slow twitch and fast twitch isoform genes must have occurred prior to the divergence of mammals and avians. We have also localized the human ventricular/slow twitch isoform gene to the short arm of human chromosome 3. Interestingly the corresponding mouse gene has been mapped to the distal region of mouse chromosome 9 which contains a conserved syntenic group of genes that map to the short arm of human chromosome 3.

Amino Acid Sequence↗

PubMed1996

Thyroid hormone represses protein kinase C isoform expression and activity in rat cardiac myocytes.

We have previously demonstrated that at least four isoforms of protein kinase C (PKC; alpha, delta, epsilon, and zeta) are expressed in neonatal rat ventricular myocytes and that development is associated with a decline in their expression. The mechanism(s) regulating PKC isoform expression in ventricular myocytes is completely unknown. The developmental decline in PKC expression occurs, in large part, during the first 2 weeks of postnatal life, while thyroid hormone levels are known to be progressively increasing. Accordingly, this study examined the influence of thyroid hormone on PKC isoform expression to determine whether thyroid hormone can be implicated as a potential physiological regulator of PKC gene expression during normal cardiac development. Hypothyroidism was induced in adult rats by surgical thyroidectomy; thyroid status was manipulated in cultured neonatal ventricular myocytes by growth in serum-free medium with varying triiodothyronine (T3) levels. In each case, hypothyroidism was verified by a 10- to 50-fold increase in steady state mRNA for beta-myosin heavy chain. In hypothyroid adult ventricular myocardium, there was a selective 60% increase in the expression of PKC epsilon protein that corresponded to an increase in maximally stimulated PKC enzyme activity with PKC epsilon substrate peptide (epsilon pep) but not with histone as substrate. Northern blot analysis revealed a 70% increase in PKC epsilon mRNA, indicating that the regulatory effects of thyroid hormone are mediated, at least in part, at the message level. In neonatal ventricular myocytes, there was a T3-dependent reduction in immunoreactivity for both PKC alpha and PKC epsilon that was associated with significant reductions in both histone- and epsilon pep-kinase activities. The concentration of T3 that half-maximally repressed PKC alpha and PKC epsilon expression was approximately 0.5 nmol/L. Thyroid hormone had no effect on PKC delta and PKC zeta expression in neonatal or adult ventricular myocytes. PKC isoform expression in cardiac fibroblasts was not influenced by variations in the thyroid hormone concentration during culture. These results provide evidence that thyroid hormone specifically represses PKC alpha and PKC epsilon in the neonatal heart and PKC epsilon in the adult heart. Thyroid hormone-induced changes in PKC may play an important permissive role in the modulation of autonomic responsiveness in ventricular cardiomyocytes.

Animals↗