Low density lipoproteins induce parasympathetic responsiveness in embryonic chick ventricular myocytes in parallel with a coordinate increase in expression of genes coding for the M2 muscarinic receptor, G alpha i2, and the acetylcholine-sensitive K+ channel.

Gadbut, Albert P.; Toupin, Darlene; Kilbourne, Edward J.; Galper, Jonas B.

doi:10.1016/s0021-9258(18)43871-9

Cited by 17 publications

(6 citation statements)

References 26 publications

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“…The data presented here and in prior studies demonstrate that induction of the cholesterol metabolic pathway increases expression of G‐α i2 , M 2 and GIRK1 (Haigh et al ., 1988; Gadbut et al ., 1994). Ligand‐binding data and Western blot analysis have suggested that levels of β‐adrenergic receptors and G‐α s are coordinately decreased by induction of the cholesterol pathway (Barnett et al ., 1989).…”

Section: Discussionmentioning

confidence: 99%

“…LPDS was prepared as described previously (Gadbut et al ., 1994). Briefly, FCS was overlaid with a solution of KBr with a final density of 1.21 g/ml followed by centrifugation in a Ti‐70 rotor at 265 000 g for 16 h at 10°C.…”

Section: Methodsmentioning

confidence: 99%

“…An aliquot containing 50 μg of membrane protein was diluted with 3× SDS‐Laemmli buffer followed by polyacrylamide gel electrophoresis on a 4–15% gradient gel (Bio‐Rad, Hercules, CA). Immunoblotting was carried out using the ECL Western blotting analysis system (Amersham Corp. Buckinghampshire, UK) as described (Gadbut et al ., 1994).…”

Section: Methodsmentioning

confidence: 99%

“…The increased responsiveness to carbamylcholine seen in heart cells following induction of cholesterol biosynthesis was associated with an increase in expression of components of the parasympathetic pathway, i.e. high affinity muscarinic receptors and the G protein α‐subunit G‐α i2 (Haigh et al ., 1988), and an increase in levels of mRNAs coding for the M 2 muscarinic receptor, G‐α i2 and the G protein‐coupled inward rectifying K + channel, GIRK1 (Gadbut et al ., 1994). The decreased responsiveness to isoproterenol following induction of cholesterol biosynthesis was associated with a coordinated decrease in components of the sympathetic response system, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…1989). Mevinolin, a highly specific inhibitor of HMG CoA reductase (Figure 1), reversed all the effects of induction of endogenous cholesterol biosynthesis on cardiac autonomic physiology and receptor, G protein and K + channel expression (Haigh et al ., 1988; Barnett et al ., 1989; Gadbut et al ., 1994). These findings suggested the existence of a program of gene expression in which components of second messenger pathways are regulated by sterol metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Induction of the cholesterol metabolic pathway regulates the farnesylation of RAS in embryonic chick heart cells: a new role for Ras in regulating the expression of muscarinic receptors and G proteins

Gadbut

1997

The EMBO Journal

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We propose a novel mechanism for the regulation of the processing of Ras and demonstrate a new function for Ras in regulating the expression of cardiac autonomic receptors and their associated G proteins. We have demonstrated previously that induction of endogenous cholesterol synthesis in cultured cardiac myocytes resulted in a coordinated increase in expression of muscarinic receptors, the G protein α-subunit, G-α i2 , and the inward rectifying K ϩ channel, GIRK1. These changes in gene expression were associated with a marked increase in the response of heart cells to parasympathetic stimulation. In this study, we demonstrate that the induction of the cholesterol metabolic pathway regulates Ras processing and that Ras regulates expression of G-α i2 . We show that in primary cultured myocytes most of the RAS is localized to the cytoplasm in an unfarnesylated form. Induction of the cholesterol metabolic pathway results in increased farnesylation and membrane association of RAS. Studies of Ras mutants expressed in cultured heart cells demonstrate that activation of Ras by induction of the cholesterol metabolic pathway results in increased expression of G-α i2 mRNA. Hence farnesylation of Ras is a regulatable process that plays a novel role in the control of second messenger pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Induction of the cholesterol metabolic pathway regulates the farnesylation of RAS in embryonic chick heart cells: a new role for Ras in regulating the expression of muscarinic receptors and G proteins

Gadbut

1997

The EMBO Journal

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TGFβ Regulates the Expression of Gαi2 via an Effect on the Localization of Ras

Ward

Gadbut

Tang

et al. 2002

Journal of Molecular and Cellular Cardiology

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Chiloscyllium plagiosum low-density lipoprotein receptor: Evolutionary conservation of five different functional domains

1996

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All five functional domains of the low-density lipoprotein (LDL) receptor were assembled in their modern form more than 450 million years ago, as revealed from the cloning and sequencing of an LDL receptor cDNA from Chiloscyllium plagiosum (banded cat shark). The shark LDL receptor has the same overall architecture as the mammalian and amphibian counterparts. Each of the seven cysteine-rich repeats in the ligand binding domain resembles its counterpart in the human LDL receptor more than it does the other repeats in the shark receptor as suggested by the presence of unique "signature" sequences, indicating that these repeats had already acquired their independent structures by the time of shark development. Furthermore, amino acid sequences of the entire ligand binding domain of shark LDL receptor show 35% identity over a stretch of 294 residues with a Lymnaea stagnalis G-protein-linked receptor (LSGLR). The region of homology between these unrelated proteins includes conservation of most of the unique characteristics of the cysteine-rich repeats of LDL receptor at the expected positions in LSGLR. The results presented are consistent with the hypothesis that all seven repeats in the ligand binding domain of LDL receptor may have been lifted directly from an ancestral gene instead of being evolutionary duplications of a single repeat recruited by the primitive LDL receptor from another gene.

show abstract

Low density lipoproteins induce parasympathetic responsiveness in embryonic chick ventricular myocytes in parallel with a coordinate increase in expression of genes coding for the M2 muscarinic receptor, G alpha i2, and the acetylcholine-sensitive K+ channel.

Cited by 17 publications

References 26 publications

Induction of the cholesterol metabolic pathway regulates the farnesylation of RAS in embryonic chick heart cells: a new role for Ras in regulating the expression of muscarinic receptors and G proteins

Induction of the cholesterol metabolic pathway regulates the farnesylation of RAS in embryonic chick heart cells: a new role for Ras in regulating the expression of muscarinic receptors and G proteins

TGFβ Regulates the Expression of Gαi2 via an Effect on the Localization of Ras

Chiloscyllium plagiosum low-density lipoprotein receptor: Evolutionary conservation of five different functional domains

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