Hypoxia-mediated down-regulation of OCTN2 and PPARrα expression in human placentas and in BeWo cells

Molecular Pharmaceutics

Volumn 8, Issue 1, 2011, Pages 117-125

  Chang, Ting Ting ^a   Shyu, Ming Kwang ^b   Huang, Min Chuan ^a   Hsu, Chen Chi ^a   Yeh, Szu Yu ^a   Chen, Mei Ru ^a   Lin, Chun Jung ^a,c  

^a NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^b NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^c NONE   (Taiwan)

Author keywords

BeWo cells; Hypoxia; OCTN2; PPARR ; Preeclampsia

Indexed keywords

AMINO ACID RECEPTOR; CARNITINE; FORSKOLIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; MESSENGER RNA; OCTN2 PROTEIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PIRINIXIC ACID; PROTEIN; RETINOID X RECEPTOR ALPHA; SYNCYTIN; UNCLASSIFIED DRUG;

ARTICLE; CANCER CELL CULTURE; CARCINOMA CELL; CHORIOCARCINOMA; CONTROLLED STUDY; DOWN REGULATION; EXPLANT; FEMALE; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPOXIA; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; MALE; PLACENTA; POLYMERASE CHAIN REACTION; PREECLAMPSIA; PRIORITY JOURNAL; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; SYNCYTIOTROPHOBLAST; WESTERN BLOTTING;

ADULT; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; BLOTTING, WESTERN; CARNITINE; CELL HYPOXIA; CELLS, CULTURED; FEMALE; FORSKOLIN; GENE EXPRESSION; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; IMMUNOHISTOCHEMISTRY; MALE; ORGANIC CATION TRANSPORT PROTEINS; PLACENTA; POLYMERASE CHAIN REACTION; PPAR ALPHA; PREGNANCY; TISSUE CULTURE TECHNIQUES;

EID: 79952979127     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp100137q     Document Type: Article

References (29)

1. Hung, T. H.; Burton, G. J. Hypoxia and reoxygenation: a possible mechanism for placental oxidative stress in preeclampsia. Taiwan J. Obstet. Gynecol. 2006, 45, 189-200. (Pubitemid 44519397)
2. Genbacev, O.; Joslin, R.; Damsky, C. H.; Pollotti, B. M.; Fisher, S. J. Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J. Clin. InVest. 1996, 97, 540-550. (Pubitemid 26039422)
3. Chelbi, S. T.; Vaiman, D. Genetic and epigenetic factors contribute to the onset of preeclampsia. Mol. Cell. Endocrinol. 2008, 282, 120-129.
4. Shih, S. C.; Claffey, K. P. Hypoxia-mediated regulation of gene expression in mammalian cells. Int. J. Exp. Pathol. 1998, 79, 347-357. (Pubitemid 29010694)
5. Caniggia, I.; Mostachfi, H.; Winter, J. Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFβ(3). J. Clin. InVest. 2000, 105, 577-587. (Pubitemid 30146504)
6. Rajakumar, A.; Brandon, H. M.; Daftary, A.; Ness, R.; Conrad, K. P. Evidence for the functional activity of hypoxia-inducible transcription factors overexpressed in preeclamptic placentae. Placenta 2004, 25, 763-769. (Pubitemid 39276941)
7. Huang, F. D.; Kung, F. L.; Tseng, Y. C.; Chen, M. R.; Chan, H. S.; Lin, C. J. Regulation of protein expression and function of OCTN2 in forskolin-induced syncytialization in BeWo Cells. Placenta 2009, 30, 187-194.
8. Knerr, I.; Weigel, C.; Linnemann, K.; Dötsch, J.; Meissner, U.; Fusch, C.; Rascher, W. Transcriptional effects of hypoxia on fusiogenic syncytin and its receptor ASCT2 in human cytotrophoblast BeWo cells and in ex vivo perfused placental cotyledons. Am. J. Obstet. Gynecol. 2003, 189, 583-588.
9. Kudo, Y.; Boyd, C. A. R.; Sargent, I. L.; Redman, C. W. G. Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in preeclampsia. Biochim. Biophys. Acta 2003, 1638, 63-71. (Pubitemid 36577373)
10. Thiele, I. G. I.; Niezen-Koning, K. E.; van Gennip, A. H.; Aarnoudse, J. G. Increased plasma carnitine concentrations in preeclampsia. Obstet. Gynecol. 2004, 103, 876-880. (Pubitemid 40458987)
11. Famularo, G.; de Simone, C.; Trinchieri, V.; Mosca, L. Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation. Ann. N.Y. Acad. Sci. 2004, 1033, 132-138. (Pubitemid 39656745)
12. Fortin, G.; Yurchenko, K.; Collette, C. L-carnitine, a diet component and organic cation transporter OCTN ligand, displays immunosuppressive properties and abrogates intestinal inflammation. Clin. Exp. Immunol. 2009, 156, 161-171.
13. Bargen-Lockner, C.; Hahn, P.; Wittmann, B. Plasma carnitine in pregnancy. Am. J. Obstet. Gynecol. 1981, 140, 412-414. (Pubitemid 11078808)
14. Arenas, J.; Rubio, J. C.; Martin, M. A.; Campos, Y. Biological roles of L-carnitine in perinatal metabolism. Early Hum. Dev. 1998, 53, S43-S50. (Pubitemid 28548701)
15. Grube, M.; Meyer zu Schwabedissen, H. M.; Präger, D.; Haney, J.; Möritz, K. U.; Meissner, K.; Rosskopf, D.; Eckel, L.; Böhm, M.; Jedlitschky, G.; Kroemer, H. K. Uptake of cardiovascular drugs into the human heart: expression, regulation, and function of the carnitine transporter OCTN2 (SLC22A5). Circulation 2006, 113, 1114-1122.
16. Wu, S. P.; Shyu, M. K.; Liou, H. H.; Gau, C. S.; Lin, C. J. Interaction between anticonvulsants and human placental carnitine transporter. Epilepsia 2004, 45, 204-210.
17. Grube, M.; Schwabedissen, H. M.; Draber, K.; Präger, D.; Möritz, K. U.; Linnemann, K.; Fusch, C.; Jedlitschky, G.; Kroemer, H. K. Expression, localization, and function of the carnitine transporter OCTN2 (slc22a5) in human placenta. Drug Metab. Dispos. 2005, 33, 31-37. (Pubitemid 40023511)
18. Rytting, E.; Audus, K. L. Effects of low oxygen levels on the expression and function of transporter OCTN2 in BeWo cells. J. Pharm. Pharmacol. 2007, 59, 1095-1102. (Pubitemid 47265356)
19. Luci, S.; Geissler, S.; König, B.; Koch, A.; Stangl, G. I.; Hirche, F.; Eder, K. PPARα agonists up-regulate organic cation transporters in rat liver cells. Biochem. Biophys. Res. Commun. 2006, 350, 704-708. (Pubitemid 44547904)
20. Maeda, T.; Wakasawa, T.; Funabashi, M.; Fukushi, A.; Fujita, M.; Motojima, K.; Tamai, I. Regulation of Octn2 transporter (SLC22A5) by peroxisome proliferator activated receptor α. Biol. Pharm. Bull. 2008, 31, 1230-1236. (Pubitemid 351871185)
21. Koch, A.; König, B.; Stangl, G. I.; Eder, K. PPAR α mediates transcriptional upregulation of novel organic cation transporters- 2 and-3 and enzymes involved in hepatic carnitine synthesis. Exp. Biol. Med. 2008, 233, 356-365. (Pubitemid 351328577)
22. Lockwood, C. J.; Yen, C. F.; Basar, M.; Kayisli, U. A.; Martel, M.; Buhimschi, I.; Buhimschi, C.; Huang, S. J.; Krikun, G.; Schatz, F. Preeclampsia-related inflammatory cytokines regulate interleukin-6 expression in human decidual cells. Am. J. Pathol. 2008, 172, 1571-1579. (Pubitemid 351793350)
23. Lazennec, G.; Canaple, L.; Saugy, D.; Wahli, W. Activation of peroxisome proliferator-activated receptors (PPARs) by their ligands and protein kinase A activators. Mol. Endocrinol. 2000, 14, 1962-1975. (Pubitemid 32055530)
24. Yessoufou, A.; Hichami, A.; Besnard, P.; Moutairou, K.; Khan, N. A. Peroxisome proliferator-activated receptor α deficiency increases the risk of maternal abortion and neonatal mortality in murine pregnancy with or without diabetes mellitus: Modulation of T cell differentiation. Endocrinology 2006, 147, 4410-4418. (Pubitemid 44268392)
25. Hubel, C. A.; McLaughlin, M. K.; Evans, R. W.; Hauth, B. A.; Sims, C. J.; Roberts, J. M. Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 h post partum. Am. J. Obstet. Gynecol. 1996, 174, 975-982. (Pubitemid 26111679)
26. Murai, J. T.; Muzykanskiy, E.; Taylor, R. N. Maternal and fetal modulators of lipid metabolism correlate with the development of preeclampsia. Metabolism 1997, 46, 963-967. (Pubitemid 27339925)
27. Narravula, S.; Colgan, S. P. Hypoxia-inducible factor 1-mediated inhibition of peroxisome proliferator-activated receptor R expression during hypoxia. J. Immunol. 2001, 166, 7543-7548. (Pubitemid 32525634)
28. Huss, J. M.; Levy, F. H.; Kelly, D. P. Hypoxia inhibits the peroxisome proliferator-activated receptor R/retinoid X receptor gene regulatory pathway in cardiac myocytes: a mechanism for O2-dependent modulation of mitochondrial fatty acid oxidation. J. Biol. Chem. 2001, 276, 27605-27612.
29. Wang, G. L.; Semenza, G. L. Characterization of hypoxiainducible factor 1 and regulation of DNA binding activity by hypoxia. J. Biol. Chem. 1993, 268, 21513-21518. (Pubitemid 23320639)