Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21817 (RyR1)
 1,154 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the mRNA distribution of three different ryanodine receptors (RyR) and of the intracellular Ca(2+)-release channel/inositol 1,4,5-trisphosphate receptor (IP3R) type 1 in the rat heart during development and aging. In situ hybridization analysis shows that RyR1 mRNA is never expressed in the heart at any of the stages examined: RyR2 mRNA is detectable in cardiomyocytes in the early embryonic stages, whereas RyR3 mRNA accumulates in cardiomyocytes around birth. IP3R mRNA appears at first in the primitive atrium at embryonic day 11 and in subsequent stages it is detectable also in a minor population of ventricular myocytes, which presumably correspond to conduction system precursors. In the adult heart, no apparent difference in hybridization signal intensity is observed between atrial and ventricular working myocytes either with RyR2, RyR3 or IP3R cRNA probes, except for myocytes of the heart conduction system, which differ from working myocytes in the intensity of the hybridization signals for each probe. Additional differences are detected in the senescent heart with the IP3R cRNA probe, which hybridizes with atrial myocytes stronger than with ventricular ones. RNase protection analysis confirms the temporal differences in RyR2 and RyR3 transcript accumulation observed during heart development and reveals a significant increase of IP3R mRNA in the atrial myocardium during aging. Thus, the composition of intracellular Ca(2+)-release channel mRNAs of the rat heart shows temporal and regional variations: such changes might reflect important differences in transcriptional regulation of these genes among myocytes.
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PMID:Regional and age-related differences in mRNA composition of intracellular Ca(2+)-release channels of rat cardiac myocytes. 915 63

In the present work, we investigated whether IGF-1 regulates the transcription of the genes encoding the L-type Ca2+ channel (DHPR) channel and RyR1 in young adult and senescent mice. To this end, a transgenic mouse model overexpressing IGF-1 exclusively in skeletal muscle (S1S2) was studied at different ages and the results were compared with wild type age-matched mice (FVB). We found that ribosomal RNA expression did not change significantly either with age or IGF-1 according to ribonuclease protection and nuclear run-on transcription assays. Transgenic overexpression of IGF-1 resulted in marked increases in skeletal muscle DHPR alpha(1S) and RyR1 mRNA in young and old mice and in enhanced DHPR alpha(1S) nuclear transcription in skeletal muscles from young mice when normalized to 28S ribosomal RNA. These results support the concept that IGF-1 regulates the expression of DHPR by modulating DHPR alpha(1S) nuclear transcription.
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PMID:Age-dependent IGF-1 regulation of gene transcription of Ca2+ channels in skeletal muscle. 1124 Jan 60

Recently, a receptor for renin was described that may be important for vascular uptake and activation of (pro)renin, thus leading to local generation of angiotensin II. To assess the in vivo relevance of this protein, we generated transgenic rats overexpressing the human renin receptor gene in smooth muscle tissue, under the control of a 16-kb fragment of the mouse smooth muscle myosin heavy chain gene [TGR(SMMHC-HRR)]. Four lines of transgenic animals were obtained. The correct pattern of expression of the transgene was confirmed by RNase protection assay and in situ hybridization. TGR(SMMHC-HRR) rats are fertile and develop normally. After 6 months of age, transgenic rats develop a cardiovascular phenotype with an elevated systolic blood pressure (137.8+/-5 versus 118.9+/-3.7 mm Hg; P=0.008), and an augmentation in heart rate (349.1+/-7.7 versus 303.1+/-16.16 bpm; P=0.023) in TGR(SMMHC-HRR) and controls, respectively. These alterations are progressively increasing with aging. Although kidney function and plasma renin were normal in TGR(SMMHC-HRR), an increase in plasma aldosterone [TGR(SMMHC-HRR) 428+/-64.9 versus 207.3+/-73.24 pg/mL in control; P=0.02] and in aldosterone/renin ratio [TGR(SMMHC-HRR) 8.04+/-2.2 versus 2.8+/-0.55 in control; P=0.03] was observed. This suggests that renin receptor overexpression has resulted in increased intraadrenal angiotensin II, thereby provoking enhanced aldosterone generation in the absence of changes in plasma renin. The rise in aldosterone may underlie, at least in part, the observed cardiovascular phenotype of TGR(SMMHC-HRR).
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PMID:Elevated blood pressure and heart rate in human renin receptor transgenic rats. 1640 65