Effects of PPAR-α agonist and IGF-1 on estrogen sulfotransferase in human vascular endothelial and smooth muscle cells

Li,Yintao; Xu,Yali; Li,Xiaobo; Qin,Yejun; Hu,Renming

doi:10.3892/mmr.2013.1483

Effects of PPAR-α agonist and IGF-1 on estrogen sulfotransferase in human vascular endothelial and smooth muscle cells

Authors:
- Yintao Li
- Yali Xu
- Xiaobo Li
- Yejun Qin
- Renming Hu
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Affiliations: Department of Endocrinology and Metabolism, Institute of Endocrinology and Diabetology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, P.R. China, Department of Pathology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Published online on: May 17, 2013 https://doi.org/10.3892/mmr.2013.1483
Pages: 133-139

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Abstract

Estrogen has a protective role in vascular functions and estrogen levels are modulated by estrogen sulfotransferase (SULT1E1). In this study, we investigated the effects of the peroxisome proliferator-activated receptor-α (PPAR-α) agonist WY14643 and insulin-like growth factor-1 (IGF-1) on the expression and activity of SULT1E1 in vascular cells. Human umbilical vein endothelial cells (HUVECs) and human umbilical artery smooth muscle cells (HUASMCs) were primarily cultured from fresh umbilical cord. SULT1E1 was highly expressed in HUVECs and HUASMCs according to immunofluorescence microscopy detection. WY14643 decreased, while IGF-1 increased, SULT1E1 mRNA and SULT1E1 protein levels, as demonstrated by RT-qPCR and western blot analysis, respectively, in the HUVECs and HUASMCs. SULT1E1 activity was indicated by counting the transformed 3H-estradiol sulfate from 3H-labeled 17β-estradiol added into the cell culture medium. The activity of SULT1E1 reduced following treatment with WY14643, whereas SULT1E1 activity was enhanced in the presence of IGF-1. The human SULT1E1 promoter-reporter plasmid was constructed. The activity of the SULT1E1 promoter increased 30-fold compared with the pGL3-basic vector. The PPAR-α agonist WY14643 downregulated, while IGF-1 upregulated, the luciferase activity of the SULT1E1 promoter. In conclusion, the PPAR-α agonist WY14643 and IGF-1 may regulate SULT1E1 expression at the transcriptional level and modulate the levels of active estrogens in endothelial cells and smooth muscle cells, thereby affecting the physiology and pathophysiology of vascular walls.

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1	Nofer JR: Estrogens and atherosclerosis: insights from animal models and cell systems. J Mol Endocrinol. 48:R13–R29. 2012. View Article : Google Scholar : PubMed/NCBI
2	Ishibashi H, Suzuki T, Suzuki S, et al: Estrogen inhibits cell proliferation through in situ production in human thymoma. Clin Cancer Res. 11:6495–6504. 2005. View Article : Google Scholar : PubMed/NCBI
3	Xu Y, Liu X, Guo F, et al: Effect of estrogen sulfation by SULT1E1 and PAPSS on the development of estrogen-dependent cancers. Cancer Sci. 103:1000–1009. 2012. View Article : Google Scholar : PubMed/NCBI
4	Tong MH, Jiang H, Liu P, Lawson JA, Brass LF and Song WC: Spontaneous fetal loss caused by placental thrombosis in estrogen sulfotransferase-deficient mice. Nat Med. 11:153–159. 2005. View Article : Google Scholar : PubMed/NCBI
5	Wada T, Ihunnah CA, Gao J, et al: Estrogen sulfotransferase inhibits adipocyte differentiation. Mol Endocrinol. 25:1612–1623. 2011. View Article : Google Scholar : PubMed/NCBI
6	Gong H, Jarzynka MJ, Cole TJ, et al: Glucocorticoids antagonize estrogens by glucocorticoid receptor-mediated activation of estrogen sulfotransferase. Cancer Res. 68:7386–7393. 2008. View Article : Google Scholar : PubMed/NCBI
7	Kodama S, Hosseinpour F, Goldstein JA and Negishi M: Liganded pregnane X receptor represses the human sulfotransferase SULT1E1 promoter through disrupting its chromatin structure. Nucleic Acids Res. 39:8392–8403. 2011. View Article : Google Scholar : PubMed/NCBI
8	Fruchart JC: Peroxisome proliferator-activated receptor-alpha (PPARalpha): at the crossroads of obesity, diabetes and cardiovascular disease. Atherosclerosis. 205:1–8. 2009. View Article : Google Scholar : PubMed/NCBI
9	Hennuyer N, Tailleux A, Torpier G, et al: PPARalpha, but not PPARgamma, activators decrease macrophage-laden atherosclerotic lesions in a nondiabetic mouse model of mixed dyslipidemia. Arterioscler Thromb Vasc Biol. 25:1897–1902. 2005. View Article : Google Scholar
10	Srivastava RA: Evaluation of anti-atherosclerotic activities of PPAR-alpha, PPAR-gamma, and LXR agonists in hyperlipidemic atherosclerosis-susceptible F(1)B hamsters. Atherosclerosis. 214:86–93. 2011. View Article : Google Scholar : PubMed/NCBI
11	Zahradka P, Yurkova N, Litchie B, Moon MC, Del Rizzo DF and Taylor CG: Activation of peroxisome proliferator-activated receptors alpha and gamma1 inhibits human smooth muscle cell proliferation. Mol Cell Biochem. 246:105–110. 2003. View Article : Google Scholar
12	Hamblin M, Chang L, Fan Y, Zhang J and Chen YE: PPARs and the cardiovascular system. Antioxid Redox Signal. 11:1415–1452. 2009. View Article : Google Scholar
13	Fang HL, Strom SC, Cai H, Falany CN, Kocarek TA and Runge-Morris M: Regulation of human hepatic hydroxysteroid sulfotransferase gene expression by the peroxisome proliferator-activated receptor alpha transcription factor. Mol Pharmacol. 67:1257–1267. 2005. View Article : Google Scholar
14	Higashi Y, Sukhanov S, Anwar A, Shai SY and Delafontaine P: IGF-1, oxidative stress and atheroprotection. Trends Endocrinol Metab. 21:245–254. 2010. View Article : Google Scholar : PubMed/NCBI
15	Higashi Y, Sukhanov S, Anwar A, Shai SY and Delafontaine P: Aging, atherosclerosis, and IGF-1. J Gerontol A Biol Sci Med Sci. 67:626–639. 2012. View Article : Google Scholar : PubMed/NCBI
16	Han Y, Qi Y, Kang J, Li N, Tian X and Yan C: Nerve growth factor promotes formation of lumen-like structures in vitro through inducing apoptosis in human umbilical vein endothelial cells. Biochem Biophys Res Commun. 366:685–691. 2008. View Article : Google Scholar
17	Vadiveloo PK, Filonzi EL, Stanton HR and Hamilton JA: G1 phase arrest of human smooth muscle cells by heparin, IL-4 and cAMP is linked to repression of cyclin D1 and cdk2. Atherosclerosis. 133:61–69. 1997. View Article : Google Scholar : PubMed/NCBI
18	Yeong P, Ning Y, Xu Y, Li X and Yin L: Tryptase promotes human monocyte-derived macrophage foam cell formation by suppressing LXRalpha activation. Biochim Biophys Acta. 1801:567–576. 2010. View Article : Google Scholar : PubMed/NCBI
19	Wang X, Spandidos A, Wang H and Seed B: PrimerBank: a PCR primer database for quantitative gene expression analysis, 2012 update. Nucleic Acids Res. 40:D1144–D1149. 2012. View Article : Google Scholar : PubMed/NCBI
20	Kushida A, Hattori K, Yamaguchi N, Kobayashi T, Date A and Tamura H: Sulfation of estradiol in human epidermal keratinocyte. Biol Pharm Bull. 34:1147–1151. 2011. View Article : Google Scholar : PubMed/NCBI
21	Xu Y, Yang X, Wang Z, et al: Estrogen sulfotransferase (SULT1E1) regulates inflammatory response and lipid metabolism of human endothelial cells via PPARgamma. Mol Cell Endocrinol. 369:140–149. 2013. View Article : Google Scholar : PubMed/NCBI
22	Lalloyer F, Wouters K, Baron M, et al: Peroxisome proliferatoractivated receptor-alpha gene level differently affects lipid metabolism and inflammation in apolipoprotein E2 knock-in mice. Arterioscler Thromb Vasc Biol. 31:1573–1579. 2011. View Article : Google Scholar
23	Chinetti G, Lestavel S, Bocher V, et al: PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med. 7:53–58. 2001. View Article : Google Scholar : PubMed/NCBI
24	Gizard F, Nomiyama T, Zhao Y, et al: The PPARalpha/p16INK4a pathway inhibits vascular smooth muscle cell proliferation by repressing cell cycle-dependent telomerase activation. Circ Res. 103:1155–1163. 2008. View Article : Google Scholar : PubMed/NCBI
25	Plutzky J: The PPAR-RXR transcriptional complex in the vasculature: energy in the balance. Circ Res. 108:1002–1016. 2011. View Article : Google Scholar : PubMed/NCBI
26	Zoete V, Grosdidier A and Michielin O: Peroxisome proliferator-activated receptor structures: ligand specificity, molecular switch and interactions with regulators. Biochim Biophys Acta. 1771:915–925. 2007. View Article : Google Scholar
27	Sukhanov S, Higashi Y, Shai SY, et al: Differential requirement for nitric oxide in IGF-1-induced anti-apoptotic, anti-oxidant and anti-atherosclerotic effects. FEBS Lett. 585:3065–3072. 2011. View Article : Google Scholar : PubMed/NCBI
28	Wang J, Razuvaev A, Folkersen L, et al: The expression of IGFs and IGF binding proteins in human carotid atherosclerosis, and the possible role of IGF binding protein-1 in the regulation of smooth muscle cell proliferation. Atherosclerosis. 220:102–109. 2012. View Article : Google Scholar : PubMed/NCBI
29	Delafontaine P, Song YH and Li Y: Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. Arterioscler Thromb Vasc Biol. 24:435–444. 2004. View Article : Google Scholar : PubMed/NCBI