Thyroid hormone regulation of transmembrane signalling in neonatal rat ventricular myocytes by selective alteration of the expression and coupling of G-protein α-subunits

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Abstract

Thyroid hormone exerts profound effects on the activity of the hormone-sensitive adenylate cyclase system in the heart. Distinct guanine nucleotide-binding regulatory proteins (G-proteins) mediate stimulatory and inhibitory influences on adenylate cyclase activity. To examine whether the effects of thyroid hormone on adenylate cyclase involve specific changes in G-protein subunit expression, the influence of tri-iodothyronine (T3) on the biosynthesis and activity of G-proteins in neonatal rat ventricular myocytes was determined. In myocytes challenged with T3 for 5 days, G(s)α levels increased by 4 ± 0.5-fold, whereas G(i)2α levels declined by more than 80%. T3 down-regulated G(i)2α mRNA by 60% within 3 days, but had no effect on G(s)α mRNA. The basis for the decline in G(i)2α mRNA was the T3-mediated suppression of G(i)2α gene transcription by 80 ± 9% within 4 h. The decline in G(i)2α mRNA in response to T3 produced a 2-fold decrease in relative rate of synthesis of G(i)2α but not in its half-life (46 ± 7 h). G(s)α synthesis was not altered by T3, but the half-life of G(s)α increased from 50 ± 6 h in control cells to 72 ± 8 h in T3-treated cells. In addition, T3 provoked the translocation of G(s)α from the cytoplasmic to the membranous compartment. Membranous G(s)α increased from 30 ± 6% to 61 ± 7% of total cellular G(s)α, whereas cytoplasmic G(s)α declined from 68 ± 6% to 33 ± 8% within 1 day of exposure to T3. T3-mediated up-regulation of G(s)α enhanced the activation of myocardial adenylate cyclase by the stimulatory pathway whereas the down-regulation of G(i)2α attenuated the deactivation of myocardial adenylate cyclase by the inhibitory pathway.

Original languageEnglish (US)
Pages (from-to)831-841
Number of pages11
JournalBiochemical Journal
Volume307
Issue number3
DOIs
StatePublished - Jan 1 1995

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Guanine Nucleotides
Protein Subunits
Thyroid Hormones
GTP-Binding Proteins
Adenylyl Cyclases
Muscle Cells
Rats
Carrier Proteins
Messenger RNA
Half-Life
Biosynthesis
Transcription
Proteins
Up-Regulation
Down-Regulation
Genes
Chemical activation
Cells
Hormones

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{0f0f38d847664907b894b6717f7bfb18,
title = "Thyroid hormone regulation of transmembrane signalling in neonatal rat ventricular myocytes by selective alteration of the expression and coupling of G-protein α-subunits",
abstract = "Thyroid hormone exerts profound effects on the activity of the hormone-sensitive adenylate cyclase system in the heart. Distinct guanine nucleotide-binding regulatory proteins (G-proteins) mediate stimulatory and inhibitory influences on adenylate cyclase activity. To examine whether the effects of thyroid hormone on adenylate cyclase involve specific changes in G-protein subunit expression, the influence of tri-iodothyronine (T3) on the biosynthesis and activity of G-proteins in neonatal rat ventricular myocytes was determined. In myocytes challenged with T3 for 5 days, G(s)α levels increased by 4 ± 0.5-fold, whereas G(i)2α levels declined by more than 80{\%}. T3 down-regulated G(i)2α mRNA by 60{\%} within 3 days, but had no effect on G(s)α mRNA. The basis for the decline in G(i)2α mRNA was the T3-mediated suppression of G(i)2α gene transcription by 80 ± 9{\%} within 4 h. The decline in G(i)2α mRNA in response to T3 produced a 2-fold decrease in relative rate of synthesis of G(i)2α but not in its half-life (46 ± 7 h). G(s)α synthesis was not altered by T3, but the half-life of G(s)α increased from 50 ± 6 h in control cells to 72 ± 8 h in T3-treated cells. In addition, T3 provoked the translocation of G(s)α from the cytoplasmic to the membranous compartment. Membranous G(s)α increased from 30 ± 6{\%} to 61 ± 7{\%} of total cellular G(s)α, whereas cytoplasmic G(s)α declined from 68 ± 6{\%} to 33 ± 8{\%} within 1 day of exposure to T3. T3-mediated up-regulation of G(s)α enhanced the activation of myocardial adenylate cyclase by the stimulatory pathway whereas the down-regulation of G(i)2α attenuated the deactivation of myocardial adenylate cyclase by the inhibitory pathway.",
author = "Suleiman Bahouth",
year = "1995",
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N2 - Thyroid hormone exerts profound effects on the activity of the hormone-sensitive adenylate cyclase system in the heart. Distinct guanine nucleotide-binding regulatory proteins (G-proteins) mediate stimulatory and inhibitory influences on adenylate cyclase activity. To examine whether the effects of thyroid hormone on adenylate cyclase involve specific changes in G-protein subunit expression, the influence of tri-iodothyronine (T3) on the biosynthesis and activity of G-proteins in neonatal rat ventricular myocytes was determined. In myocytes challenged with T3 for 5 days, G(s)α levels increased by 4 ± 0.5-fold, whereas G(i)2α levels declined by more than 80%. T3 down-regulated G(i)2α mRNA by 60% within 3 days, but had no effect on G(s)α mRNA. The basis for the decline in G(i)2α mRNA was the T3-mediated suppression of G(i)2α gene transcription by 80 ± 9% within 4 h. The decline in G(i)2α mRNA in response to T3 produced a 2-fold decrease in relative rate of synthesis of G(i)2α but not in its half-life (46 ± 7 h). G(s)α synthesis was not altered by T3, but the half-life of G(s)α increased from 50 ± 6 h in control cells to 72 ± 8 h in T3-treated cells. In addition, T3 provoked the translocation of G(s)α from the cytoplasmic to the membranous compartment. Membranous G(s)α increased from 30 ± 6% to 61 ± 7% of total cellular G(s)α, whereas cytoplasmic G(s)α declined from 68 ± 6% to 33 ± 8% within 1 day of exposure to T3. T3-mediated up-regulation of G(s)α enhanced the activation of myocardial adenylate cyclase by the stimulatory pathway whereas the down-regulation of G(i)2α attenuated the deactivation of myocardial adenylate cyclase by the inhibitory pathway.

AB - Thyroid hormone exerts profound effects on the activity of the hormone-sensitive adenylate cyclase system in the heart. Distinct guanine nucleotide-binding regulatory proteins (G-proteins) mediate stimulatory and inhibitory influences on adenylate cyclase activity. To examine whether the effects of thyroid hormone on adenylate cyclase involve specific changes in G-protein subunit expression, the influence of tri-iodothyronine (T3) on the biosynthesis and activity of G-proteins in neonatal rat ventricular myocytes was determined. In myocytes challenged with T3 for 5 days, G(s)α levels increased by 4 ± 0.5-fold, whereas G(i)2α levels declined by more than 80%. T3 down-regulated G(i)2α mRNA by 60% within 3 days, but had no effect on G(s)α mRNA. The basis for the decline in G(i)2α mRNA was the T3-mediated suppression of G(i)2α gene transcription by 80 ± 9% within 4 h. The decline in G(i)2α mRNA in response to T3 produced a 2-fold decrease in relative rate of synthesis of G(i)2α but not in its half-life (46 ± 7 h). G(s)α synthesis was not altered by T3, but the half-life of G(s)α increased from 50 ± 6 h in control cells to 72 ± 8 h in T3-treated cells. In addition, T3 provoked the translocation of G(s)α from the cytoplasmic to the membranous compartment. Membranous G(s)α increased from 30 ± 6% to 61 ± 7% of total cellular G(s)α, whereas cytoplasmic G(s)α declined from 68 ± 6% to 33 ± 8% within 1 day of exposure to T3. T3-mediated up-regulation of G(s)α enhanced the activation of myocardial adenylate cyclase by the stimulatory pathway whereas the down-regulation of G(i)2α attenuated the deactivation of myocardial adenylate cyclase by the inhibitory pathway.

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