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Modified high-density lipoprotein modulates aldosterone release through scavenger receptors via extra cellular signal-regulated kinase and Janus kinase-dependent pathways

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Abstract

Patients with type 2 diabetes (T2D) manifest significant abnormalities in lipoprotein structure and function. The deleterious impact of oxidative and glycoxidative modifications on HDL-mediated atheroprotective, antiinflammatory, and antioxidative phenomena has been well established. However, the biological effects of modified HDL on adrenal steroidogenesis—which could reveal a pathophysiological link to the overactivity of the renin–angiotensin–aldosterone system and its adverse cardiovascular consequences often observed in T2D—are not well delineated. We studied the role of modified HDL on aldosterone release from adrenocortical carcinoma cells (NCI-H295R). In vitro modifications of native HDL were performed in the presence of glucose for glycoxidized HDL (glycoxHDL) and sodium hypochlorite for oxidized HDL. Angiotensin II (AngII)-sensitized H295R cells were treated with lipoproteins for 24 h, and supernatant was used to measure aldosterone release. Both native and modified HDL augmented the steroid release from AngII-sensitized cells, with glycoxHDL having the greatest impact. Both the modified forms of HDL induced a significant increase in scavenger receptor expression and employed protein kinase C as well as extracellular signal-regulated kinase as downstream effectors of aldosterone release. Native HDL and modified HDL required Janus kinase-2 for combating increased demand in steroidogenesis. Therefore, our data support the hypothesis that diabetes-induced modification of HDL may promote adrenocortical aldosterone secretion via different signal transduction pathways. This significant influence on multiple signaling mechanisms could be targeted for future research to implement novel therapeutic trials.

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References

  1. 1.

    Sviridov D, Nestel P (2002) Dynamics of reverse cholesterol transport: protection against atherosclerosis. Atherosclerosis 161(2):245–254

  2. 2.

    Gotto AM, Brinton EA Jr (2004) Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease. J Am Coll Cardiol 43:717–724

  3. 3.

    Kontush A, Chapman JM (2006) Functionally defective HDL: a new therapeutic target at the crossroads of dyslipidemia, inflammation and atherosclerosis. Pharmacol Rev 58:342–374

  4. 4.

    Azhar S, Leers-Sucheta S, Reaven E (2003) Cholesterol uptake in adrenal and gonadal tissues: the SR-BI and ‘selective’ pathway connection. Front Biosci 8:s998–s1029

  5. 5.

    Hu J, Zhang Z, Shen WJ, Azhar S (2010) Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones. Nutr Metab 7(47):1–25

  6. 6.

    Cherradi N, Bideau M, Arnaudeau S, Demaurex N, James RW, Azhar S et al (2001) Angiotensin II promotes selective uptake of high density lipoprotein cholesterol esters in bovine adrenal glomerulosa and human adrenocortical carcinoma cells through induction of scavenger receptor class B type I. Endocrinology 142:4540–4549

  7. 7.

    Krug AW, Kopprasch S, Ziegler CG, Dippong S, Catar RA, Bornstein SR et al (2007) Aldosterone rapidly induces leukocyte adhesion to endothelial cells: a new link between aldosterone and arteriosclerosis? Hypertension 50:e156–e157

  8. 8.

    Krug AW, Ehrhart-Bornstein M (2008) Aldosterone and metabolic syndrome: is increased aldosterone in metabolic syndrome patients an additional risk factor? Hypertension 51:1252–1258

  9. 9.

    Fujita T (2008) Aldosterone in salt sensitive hypertension and metabolic syndrome. J Mol Med 86:729–734

  10. 10.

    Henriksen EJ (2007) Improvement of insulin sensitivity by antagonism of the renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol 293:R974–R980

  11. 11.

    Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ et al (2005) Intensive diabetes treatment and cardiovascular disease in patients with type I diabetes. N Engl J Med 353:2643–2653

  12. 12.

    Graessler J, Pietzsch J, Westendorf T, Julius U, Bornstein SR, Kopprasch S (2007) Glycoxidised LDL isolated from subjects with impaired glucose tolerance increases CD36 and peroxisome proliferator-activator receptor γ gene expression in macrophages. Diabetologia 50:1080–1088

  13. 13.

    Veiraiah A (2005) Hyperglycemia, lipoprotein glycation, and vascular disease. Angiology 56:431–438

  14. 14.

    Toshima S, Hasegawa A, Kurabayashi M, Itabe H, Takano T, Sugano J et al (2000) Circulating oxidized low density lipoprotein levels: a biochemical risk marker for coronary heart disease. Arterioscler Thromb Vasc Biol 20:2243–2247

  15. 15.

    Kopprasch S, Pietzsch J, Kuhlisch E, Fuecker K, Temelkova-Kurktchiev T, Hanefeld M et al (2002) In vivo evidence of increased oxidation of circulating LDL in impaired glucose tolerance. Diabetes 51:3102–3106

  16. 16.

    Ansurudeen I, Pietzsch J, Graessler J, Ehrhart-Bornstein M, Saha S, Bornstein SR et al (2010) Modulation of adrenal aldosterone release by oxidative modification of low-density lipoprotein. Am J Hypertens 23(10):1061–1068

  17. 17.

    Kopprasch S, Pietzsch J, Ansurudeen I, Graessler J, Krug AW, Ehrhart-Bornstein M et al (2009) Prediabetic and diabetic in vivo modification of circulating low density lipoprotein attenuates its stimulatory effect on adrenal aldosterone and cortisol secretion. J Endocrinol 200:45–52

  18. 18.

    Hoang A, Murphy AJ, Coughlan MT, Thomas MC, Forbes JM, O’Brien R et al (2007) Advanced glycation of apolipoprotein A-I impairs its anti-atherogenic properties. Diabetologia 50(8):1770–1779

  19. 19.

    Nobecourt E, Davies MJ, Brown BE, Curtiss LK, Bonnet DJ, Charlton F et al (2007) The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin: cholesterol acyltransferase. Diabetologia 50(3):643–653

  20. 20.

    Mastorikou M, Mackness B, Liu Y, Mackness M (2008) Glycation of paraoxonase-1 inhibits its activity and impairs the ability of high density lipoprotein to metabolize membrane lipid hydroperoxides. Diabet Med 25:1049–1055

  21. 21.

    Goodfriend TL, Egan B, Stepniakowski K, Ball DL (1995) Relationships among plasma aldosterone, high-density lipoprotein cholesterol, and insulin in humans. Hypertension 25:30–36

  22. 22.

    Bochud M, Nussberger J, Bovet P, Maillard MR, Elston RC, Paccaud F et al (2006) Plasma aldosterone is independently associated with the metabolic syndrome. Hypertension 48:239–245

  23. 23.

    Fallo F, Veglio F, Bertello C, Sonino N, Della MP, Ermani M et al (2006) Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab 91:454–459

  24. 24.

    Kathiresan S, Larson MG, Benjamin EJ, Corey D, Murabito JM, Fox CS et al (2005) Clinical and genetic correlates of serum aldosterone in the community: the Framingham heart study. Am J Hypertens 18:657–665

  25. 25.

    Xing Y, Cohen A, Rothblat G, Sankaranarayanan S, Weibel G, Royer L et al (2011) Aldosterone production in human adrenocortical cells is stimulated by high-density lipoprotein 2 (HDL2) through increased expression of aldosterone synthase (CYP11B2). Endocrinology 152:751–763

  26. 26.

    Pietzsch J, Subat S, Nitzsche S, Leonhardt W, Schentke KU, Hanefeld M (1995) Very fast ultracentrifugation of serum lipoproteins: influence on lipoprotein separation and composition. Biochim Biophys Acta 1254:77–88

  27. 27.

    Maeba R, Shimasaki H, Ueta N (1994) Conformational changes in oxidized LDL recognized by mouse peritoneal macrophages. Biochim Biophys Acta 1215:79–86

  28. 28.

    Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG et al (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478

  29. 29.

    Yagi K (1976) A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 15:212–216

  30. 30.

    Laemmly UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

  31. 31.

    Younis N, Charlton-Menys V, Sharma R, Soran H, Durrington PN (2009) Glycation of LDL in non-diabetic people: small dense LDL is preferentially glycated both in vivo and in vitro. Atherosclerosis 202:162–168

  32. 32.

    Braschi S, Geoffrion M, Nguyen A, Gaudreau Y, Milne RW (2006) The expression of apolipoprotein B epitopes is normal in LDL of diabetic and end-stage renal disease patients. Diabetologia 49:1394–1401

  33. 33.

    Younis N, Sharma R, Soran H, Charlton-Menys V, Elseweidy M, Durrington PN (2008) Glycation as an atherogenic modification of LDL. Curr Opin Lipidol 19(4):378–384

  34. 34.

    Nieland TJF, Chroni A, Fitzgerald ML, Maliga Z, Zannis VI, Kirchhausen T et al (2004) Cross-inhibition of SR-BI- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and glyburide. J Lipid Res 45:1256–1265

  35. 35.

    Osada Y, Shiratsuchi A, Nakanishi Y (2006) Involvement of mitogen activated protein kinases in class B scavenger receptor I-induced phagocytosis of apoptotic cells. Exp Cell Res 312(10):1820–1830

  36. 36.

    Marshall CJ (1994) MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr Opin Genet Dev 4(1):82–89

  37. 37.

    Mendez AJ, Oram JF, Bierman EL (1991) Protein kinase C as a mediator of high density lipoprotein receptor-dependent efflux of intracellular cholesterol. J Biol Chem 266(16):10104–10111

  38. 38.

    Tian Y, Smith RD, Balla T, Catt KJ (1998) Angiotensin II activates mitogen-activated protein kinase via protein kinase C and Ras/Raf-1 kinase in bovine adrenal glomerulosa cells. Endocrinology 139(4):1801–1809

  39. 39.

    Nofer JR, Fobker M, Höbbel G, Voss R, Wolinska I, Tepel M et al (2000) Activation of phosphatidylinositol-specific phospholipase C by HDL-associated lysosphingolipid: involvement in mitogenesis but not in cholesterol efflux. Biochemistry 39:15199–151207

  40. 40.

    Darnell JE Jr (1997) STATs and gene regulation. Science 277:1630–1635

  41. 41.

    Li J, Feltzer RE, Dawson KL, Hudson EA, Clark BJ (2003) Janus kinase 2 and calcium are required for angiotensin II-dependent activation of steroidogenic acute regulatory protein transcription in H295R human adrenocortical cells. J Biol Chem 278(52):52355–52362

  42. 42.

    Leung PS, Carlsson PO (2001) Tissue renin-angiotensin system: its expression, localization, regulation and potential role in the pancreas. J Mol Endocrinol 26(3):155–164

  43. 43.

    Chu YK, Leung PS (2009) Angiotensin II in type 2 diabetes mellitus. Curr Protein Pept Sci 10:75–84

  44. 44.

    Willenberg HS, Schinner S, Ansurudeen I (2008) New mechanisms to control aldosterone synthesis. Horm Metab Res 40:435–441

  45. 45.

    Brunham LR, Kruit JK, Verchere CB, Hayden MR (2008) Cholesterol in islet dysfunction and type 2 diabetes. J Clin Invest 118:403–408

  46. 46.

    Klein RL, Laimins M, Lopes-Virella MF (1995) Isolation, characterization, and metabolism of the glycated and nonglycated subfractions of low-density lipoproteins isolated from type I diabetic patients and nondiabetic subjects. Diabetes 44(9):1093–1098

  47. 47.

    Thorne RF, Mhaidat NM, Ralston KJ, Burns GF (2007) CD36 is a receptor for oxidized high density lipoprotein: implications for the development of atherosclerosis. Fed Eur Biochem Soc 581(6):1227–1232

  48. 48.

    Pilon A, Martin G, Bultel-Brienne S, Junquero D, Delhon A, Fruchart JC et al (2003) Regulation of scavenger receptor BI and the LDL receptor by activators of aldosterone production, angiotensin II and PMA, in the human NCI-H295R adrenocortical cell line. Biochemica et Biophysica Acta 1631:218–228

  49. 49.

    Martinat N, Crépieux P, Reiter E, Guillou F (2005) Extracellular signal-regulated kinases (ERK)1, 2 are required for luteinizing hormone (LH)-induced steroidogenesis in primary Leydig cells and control steroidogenic acute regulatory (StAR) expression. Reprod Nutr Dev 45:101–108

  50. 50.

    Ansurudeen I, Willenberg HS, Kopprasch S, Krug AW, Ehrhart-Bornstein M, Bornstein SR (2009) Endothelial factors mediate aldosterone release via PKA-independent pathways. Mol Cell Endocrinol 300(1–2):66–70

  51. 51.

    Grewal T, de Diego I, Kirchhoff MF, Tebar F, Heeren J, Rinninger F et al (2003) High density lipoprotein-induced signaling of the MAPK pathway involves scavenger receptor type BI-mediated activation of Ras. J Biol Chem 278:16478–16481

  52. 52.

    Foster RH (2004) Reciprocal influences between the signalling pathways regulating proliferation and steroidogenesis in adrenal glomerulosa cells. J Mol Endocrinol 32(3):893–902

  53. 53.

    Rütti S, Ehses JA, Sibler RA, Prazak R, Rohrer L, Georgopoulos S et al (2009) Low- and high-density lipoproteins modulate function, apoptosis, and proliferation of primary human and murine pancreatic β cells. Endocrinology 150(10):4521–4524

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Acknowledgment

The authors thank Martina Kohl, Sigrid Nitzsche, and Eva Schubert for their excellent technical support. This work was supported by the Deutsche Forschungsgemeinschaft (KFO 252 to SRB).

Conflict of interest

The authors declare that there is no conflict of interest.

Author information

Correspondence to Sarama Saha.

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Saha, S., Graessler, J., Schwarz, P.E.H. et al. Modified high-density lipoprotein modulates aldosterone release through scavenger receptors via extra cellular signal-regulated kinase and Janus kinase-dependent pathways. Mol Cell Biochem 366, 1–10 (2012) doi:10.1007/s11010-012-1274-2

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Keywords

  • HDL
  • Aldosterone
  • Glycoxidation
  • Oxidation
  • Mitogen activated protein kinase
  • Janus kinase