Gene Activation, Apolipoprotein A‐I/High Density Lipoprotein, Atherosclerosis Prevention and Longevity

Luoma, P. V.

doi:10.1111/j.1600-0773.1997.tb00032.x

Cited by 40 publications

(29 citation statements)

References 58 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The RNA was reverse-transcribed with a first strand cDNA synthesis kit using pd(N) 6 primer (Amersham Pharmacia Biotech) according to manufacturer's protocol. 3 l of this solution was amplify using PCR primed with a forward primer 5Ј-CCTGATGAATG-CTCATCCG-3Ј and reverse primer 5Ј-AAGCATTCTGCCGACATGG-3Ј homologous to the CAT gene.…”

Section: Sds-polyacrylamide Gel Electrophoresis and Westernmentioning

confidence: 99%

“…The anti-atherogenic properties of apoA-I alone or as part of HDL underlie their inverse correlation with the incidence of ischemic cardiovascular disease, the number 1 cause of premature death in modern societies (3,4). The cardioprotective actions of apoA-I or HDL arises from their participation in a normal physiologic process, so called "reverse cholesterol transport" (5,6). ApoA-I acts as a cofactor to facilitate an interaction between HDL particles and the cell membrane.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Epidermal Growth Factor Induction of Apolipoprotein A-I Is Mediated by the Ras-MAP Kinase Cascade and Sp1

Zheng¹,

Matsubara²,

Diao³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Insulin induces apolipoprotein A-I, apoA-I gene transcription via a membrane receptor with intrinsic tyrosine kinase activity. This finding prompted us to ask whether the gene is stimulated by epidermal growth factor (EGF), EGF a peptide hormone that binds to another member of the receptor superfamily with tyrosine kinase activity. Our data showed that like insulin, EGF increased abundance of apoA-I protein and transcription of the gene in human hepatoma, Hep G2 cells. The effects of both hormones appeared direct because their induction of apoA-I gene transcription was not affected by the protein synthesis inhibitor, cycloheximide. Although both insulin and EGF stimulate apoA-I expression, each hormone binds to a distinct membrane receptor thus suggesting differential intracellular signaling. Therefore, we used a panel of inhibitors to define the pathway(s) that mediate the actions of these hormones. Whereas, the actions of EGF required only the Ras-mitogen-activated protein, MAP kinase, those of insulin were mediated by equal participation of both the Ras-MAP kinase and protein kinase C, PKC cascades. Despite differences in signaling pathways triggered by each hormone receptor, the activation of apoA-I transcription required the participation of a single transcription factor, Sp1. Furthermore, EGF induction of transcription was attenuated by mutating the MAP kinase site at amino acid, Thr 266 rendering Sp1 phosphorylation deficient. In summary, EGF stimulation of apoA-I expression is mediated solely by the Ras-MAP kinase cascade and enhanced activity of this pathway requires Sp1 with an intact phosphorylation site at Thr 266 . However, insulin induction of this gene is different and requires both Ras-MAP kinase and PKC pathways but their actions are also mediated by Sp1.

show abstract

Section: Sds-polyacrylamide Gel Electrophoresis and Westernmentioning

confidence: 99%

mentioning

confidence: 99%

Epidermal Growth Factor Induction of Apolipoprotein A-I Is Mediated by the Ras-MAP Kinase Cascade and Sp1

Zheng¹,

Matsubara²,

Diao³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…As a cofactor, apo AI enhances the activity of lecithin cholesterol acyltransferase, which promotes 'reverse cholesterol transport' (RCT; Dobiasova & Frohlich 1998), whereby cholesterol is transported from extra-hepatic cells to the liver for excretion in the form of bile salts or free cholesterol (Miller et al 1985, Barter & Rye 1996b. Therefore, increased RCT lowers total cholesterol (Fielding & Fielding 1995), and apo AI levels inversely correlate to the incidence of atherosclerotic cardiovascular diseases (Rubin et al 1991, Barter & Rye 1996a, Luoma 1997. Owing to the pivotal role of apo AI in the functions of HDL particles, it is critical to identify mechanisms underlying either stimulation or inhibition of apo AI gene expression.…”

Section: Introductionmentioning

confidence: 99%

Cyclosporin A inhibits apolipoprotein AI gene expression

Zheng

Wong²

2006

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Cyclosporin A (CsA), a calcineurin inhibitor, has been widely used as an immunosuppressant, and is known to induce hyperlipidemia and dyslipoproteinemia with low levels of high-density lipoprotein (HDL). Since apolipoprotein AI (apo AI) is a major protein component of HDL particles and reduction of apo AI results in low levels of HDL, we hypothesized that CsA inhibits apo AI gene expression contributing to its lipid effects. Therefore, we first measured the serum apo AI protein levels in rats with or without CsA treatment, and found that both serum apo AI protein and liver apo AI mRNA levels were significantly reduced in response to CsA treatment. In stably transfected Hep G2 cells harboring an apo AI-474-CAT reporter gene, we found that intracellular calcium mobilization by A23187 a calcium ionophore stimulated apo AI gene expression and the calcineurin inhibitors, CsA and FK605, selectively inhibited this stimulation. Therefore, we conclude that activation of the calcineurin pathway by intracellular calcium mobilization stimulates apo AI gene expression and calcineurin inhibition by CsA results in reduced apo AI gene expression.

show abstract

“…The knowledge that apo AI alone or as part of HDL has antiatherogenic properties (Miller 1987, Barter & Rye 1996, Luoma 1997 provides the rationale for many investigators to examine the specific factors that regulate expression of the gene. A better understanding of how the gene is regulated will help us design new therapies to manipulate expression of the protein and thus augment RCT.…”

Section: Introductionmentioning

confidence: 99%

Hormonal regulation of apolipoprotein AI

Hargrove¹,

Junco²,

Wong³

1999

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Apolipoprotein AI (apo AI) is the major protein component of the serum high-density lipoprotein (HDL) particles. The antiatherogenic properties of apo AI alone or as part of HDL and their inverse correlation with the incidence of coronary heart disease underlie the clinical importance of the protein. A detailed understanding of the mechanisms by which apo AI is regulated will help us develop new and better ways to manipulate expression of the protein. Although there are many factors that influence apo AI expression, endogenous hormones are attractive because simple changes in abundance of these compounds will alter gene activity. Hormones belonging to the thyroid/steroid family that influence activity of the gene include thyroid hormone, glucocorticoids, gender-specific steroids and retinoic acid. Whereas thyroid, glucocorticoid and estradiol enhance activity of the gene, retinoic acid and androgens decrease it. The mechanisms that mediate the effects of the hormones include direct effects of the ligand and nuclear receptor complex on gene activity. However, indirect means involving the participation of transcription factors other than the hormone receptors are also possible. In summary, members of the same hormone family may have different mechanisms that mediate their activities on apo AI gene activity.

show abstract

Gene Activation, Apolipoprotein A‐I/High Density Lipoprotein, Atherosclerosis Prevention and Longevity

Cited by 40 publications

References 58 publications

Epidermal Growth Factor Induction of Apolipoprotein A-I Is Mediated by the Ras-MAP Kinase Cascade and Sp1

Epidermal Growth Factor Induction of Apolipoprotein A-I Is Mediated by the Ras-MAP Kinase Cascade and Sp1

Cyclosporin A inhibits apolipoprotein AI gene expression

Hormonal regulation of apolipoprotein AI

Contact Info

Product

Resources

About