Insulin-Like Growth Factor-I Regulation of Hepatic Scavenger Receptor Class BI

Cao, Wen; Murao, Koji; Imachi, Hitomi; Yu, Xiao; Dobashi, Hiroaki; Yoshida, Kazuya; Muraoka, Tomie; Kotsuna, Noriko; Nagao, Sachi; Wong, Norman C.W.; Ishida, Toshihiko

doi:10.1210/en.2004-0330

Cited by 29 publications

(20 citation statements)

References 50 publications

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“…And, in a series of studies, we demonstrated that PI3-kinase is essentially required for the induction of phase II detoxifying enzymes (Kang et al, 2000(Kang et al, , 2001(Kang et al, , 2003a. Signaling pathways downstream of PI3-kinase affect cell growth, survival, and motility, and IR-HCCs treated with IGF-1 showed transient PI3-kinase activation, which is consistent with previous studies (Cao et al, 2004). Either chemical inhibition or p85 subunit transfection suppressed C/EBP␤ activation and GST␣ expression by IGF-1 in IR-HCCs.…”

Section: Discussionsupporting

confidence: 91%

Induction of Glutathione Transferase in Insulin-Like Growth Factor Type I Receptor-Overexpressed Hepatoma Cells

Lee

Han²,

Yang³

et al. 2007

Mol Pharmacol

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Insulin-like growth factor type I receptor (IGF-IR) is frequently overexpressed in human hepatocellular carcinoma cells (HCC), and this overexpression has been correlated with increased tumor growth. The protective response of HCC to reactive oxygen species (ROS) produced by chemotherapeutic agents is mediated with the induction of phase II detoxifying genes including glutathione transferase (GST). To understand the roles of IGF-IR overexpression in HCC in terms of its detoxifying effect on ROS and conferred resistance to chemotherapy, we analyzed whether IGF-IR overexpressions affect IGF-1-inducible GST expression. GST␣ was induced by exposure to IGF-1 in IGF-IR cells but not in cells expressing normal levels of IGF-IR. Furthermore, IGF-IR-overexpressed HCCs (IR-HCC) are more resistant to doxorubicin than control HCC cells, which was associated with the increased GST induction by IGF-1. Molecular analyses using GSTA2 promoter supported the involvement of xenobiotic response element (XRE) in GST␣ induction. IGF-1 caused the nuclear translocation of CCAAT/ enhancer-binding protein ␤ (C/EBP␤), which might be responsible for XRE activation. In addition, IGF-1 increased the activities of phosphatidylinositol 3-kinase (PI3-kinase) and extracellular signal-regulated kinase in IR-HCCs. Moreover, the inhibition of PI3-kinase completely abolished the nuclear translocation of C/EBP␤ and the up-regulation of GST␣ protein in IR-HCC treated with IGF-1. However, specific inhibitors against extracellular signal-regulated kinase, c-Jun N-terminal kinase, or p38 kinase did not alter IGF-1-inducible GST␣ expression. These results provide evidence that one of the pathological consequences of IGF-IR overexpression in HCCs is the potentiation of GST␣ inducibility by IGF-1. Moreover, this potentiation of GST may be associated with decreased susceptibility to chemotherapeutic agents such as doxorubicin.

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Section: Discussionsupporting

confidence: 91%

Induction of Glutathione Transferase in Insulin-Like Growth Factor Type I Receptor-Overexpressed Hepatoma Cells

Lee

Han²,

Yang³

et al. 2007

Mol Pharmacol

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“…These studies indicate that cellular migration is most impaired by changes in intracellular cholesterol content, whereas the contractile response to angiotensin II is affected by TG accumulation. receptor in fibroblasts (65) and HepG2 cells (16), we expected it to be reduced. No changes in protein content of this receptor were observed; however, we examined it after 7 days, and studies in fibroblasts and hepatic cells were done after shortterm exposure to IGF-1.…”

Section: Discussionmentioning

confidence: 97%

IGF-1 induces rat glomerular mesangial cells to accumulate triglyceride

Berfield¹,

Chait²,

Oram³

et al. 2006

American Journal of Physiology-Renal Physiology

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Rat glomerular mesangial cells (MC) become lipid-laden foam cells when they are exposed to IGF-1. IGF-1 increased accumulation of triglyceride (TG) 2.5-fold in MC after 7 days. TG accumulation resulted from enhanced macropinocytosis and decreased efflux secondary to a 40-50% reduction in peroxisome proliferator-activated receptor (PPAR)-delta (PPARdelta). There was no evidence of primary or secondary changes in cholesterol or TG synthesis, increased uptake by LDL or scavenger receptors, or reduced efflux via ATP-binding cassette A-1. Although the lipid moiety taken up can be influenced by the concentration of cholesterol or TG in the medium, in standard medium MC preferentially accumulate TG. TG-rich MC foam cells fail to contract in response to angiotensin II (Berfield AK, Andress DL, and Abrass CK. Kidney Int 62: 1229-1237, 2002); however, their migratory response to IGF binding protein-5 is unaffected. This differs from cholesterol loading, which impairs both phagocytosis and migration. These findings have important implications for understanding the mechanisms that contribute to lipid accumulation in MC and the functional consequences of different forms of foam cells. These observations are relevant to understanding vascular disease and progressive renal diseases that are accelerated by abnormalities in lipid metabolism.

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“…SR-BI mediates the high affinity binding of HDL and the selective uptake of HDL-derived lipids into cells (28). It has been shown in in vitro studies with the human hepatoma cell line HepG2 that IGF1 downregulates the expression of SR-BI (29). Thus, it is possible to speculate that a reduction in circulating IGF1 levels may result in the upregulation of SR-BI leading to an increased HDL-C uptake by the liver and a decrease in circulating HDL-C concentration.…”

Section: Discussionmentioning

confidence: 99%

Positive association between plasma IGF1 and high-density lipoprotein cholesterol levels in adult nondiabetic subjects

Succurro

Arturi²,

Grembiale³

et al. 2010

European Journal of Endocrinology

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Aims: Low IGF1 levels have been associated with an increased cardiovascular risk. It is unknown however whether IGF1 mediates the atherosclerotic process by modulating high-density lipoprotein cholesterol (HDL-C) independently from confounders. To address this issue, we evaluated the association between IGF1 levels and HDL-C in nondiabetic subjects. Methods: A cross-sectional analysis was used in the context of the CAtanzaro MEtabolic RIsk factors Study. One thousand and four participants (aged 20-69 years), for whom HDL-C and IGF1 measurements were available, were eligible for the study. Results: After adjusting for gender and age, IGF1 levels were positively correlated with HDL-C, and negatively correlated with body mass index (BMI), waist circumference, blood pressure (BP), triglyceride, fasting insulin, and homeostasis model assessment (HOMA). In a logistic regression model adjusted for age and gender, IGF1 in the lowest tertile (!125 ng/ml) was associated with an increased risk of having low HDL-C (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.4-3.0; PZ4!10 K5 ) compared with the highest tertile (O186 ng/ml). When BMI, waist circumference, total cholesterol, triglyceride, and HOMA index were added to the model, IGF1 remained significantly associated with increased risk of low HDL-C (OR 1.52, 95% CI 1.01-2.31; PZ0.04). A stepwise multivariate regression analysis in a model including age, gender, BMI, total cholesterol, triglycerides, IGF1, HOMA, and BP showed that the variables significantly associated with HDL-C were gender (P!0.0001), triglycerides (P!0.0001), total cholesterol (P!0.0001), BMI (P!0.0001), IGF1 levels (P!0.0001), and HOMA (PZ0.001), accounting for 32.6% of its variation. Conclusions: These data provide evidence that IGF1 may be an independent modulator for HDL-C in nondiabetic individuals.

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Insulin-Like Growth Factor-I Regulation of Hepatic Scavenger Receptor Class BI

Cited by 29 publications

References 50 publications

Induction of Glutathione Transferase in Insulin-Like Growth Factor Type I Receptor-Overexpressed Hepatoma Cells

Induction of Glutathione Transferase in Insulin-Like Growth Factor Type I Receptor-Overexpressed Hepatoma Cells

IGF-1 induces rat glomerular mesangial cells to accumulate triglyceride

Positive association between plasma IGF1 and high-density lipoprotein cholesterol levels in adult nondiabetic subjects

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