title: Curcumin attenuates high glucose-induced podocyte apoptosis by regulating functional connections between caveolin-1 phosphorylation and ROS.
abstract: OBJECTIVE
  Caveolin-1 (cav-1) is a major multifunctional scaffolding protein of caveolae. Cav-1 is primarily expressed in mesangial cells, renal proximal tubule cells and podocytes in kidneys. Recent evidence shows that the functional connections between cav-1 and ROS play a key role in many diseases. In this study we investigated whether regulating the functional connections between cav-1 and ROS in kidneys contributed to the beneficial effects of curcumin in treating diabetic nephropathy in vitro and in vivo.
  
  
  METHODS
  Cultured mouse podocytes (mpc5) were incubated in a high glucose (HG, 30 mmol/L) medium for 24, 48 or 72 h. Male rats were injected with STZ (60 mg/kg, ip) to induce diabetes. ROS generation, SOD activity, MDA content and caspase-3 activity in the cultured cells and kidney cortex homogenate were determined. Apoptotic proteins and cav-1 phosphorylation were analyzed using Western blot analyses.
  
  
  RESULTS
  Incubation in HG-containing medium time-dependently increased ROS production, oxidative stress, apoptosis, and cav-1 phosphorylation in podocytes. Pretreatment with curcumin (1, 5, and 10 μmol/L) dose-dependently attenuated these abnormalities in HG-treated podocytes. Furthermore, in HG-containing medium, the podocytes transfected with a recombinant plasmid GFP-cav-1 Y14F (mutation at a cav-1 phosphorylation site) exhibited significantly decreased ROS production and apoptosis compared with the cells transfected with empty vector. In diabetic rats, administration of curcumin (100 or 200 mg/kg body weight per day, ig, for 8 weeks) not only significantly improved the renal function, but also suppressed ROS levels, oxidative stress, apoptosis and cav-1 phosphorylation in the kidneys.
  
  
  CONCLUSIONS
  Curcumin attenuates high glucose-induced podocyte apoptosis in vitro and diabetic nephropathy in vivo partly through regulating the functional connections between cav-1 phosphorylation and ROS.
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Ji-nan 250033, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Sun
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Ji-nan 250033, China.
authors.forename: Xiang-Chun
authors.initials: XC
authors.lastname: Liu
authors.affiliation: Chinese Medicine Hospital of Linyi City, Linyi 273400, China.
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Chen
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Ji-nan 250033, China.
authors.forename: Guang-Ju
authors.initials: GJ
authors.lastname: Guan
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Ji-nan 250033, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051242:Caveolin 1 / Q000378:metabolism*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D010766:Phosphorylation; D050199:Podocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D051242:Caveolin 1; D017382:Reactive Oxygen Species; D003474:Curcumin; D005947:Glucose
references.citation: PLoS One. 2014;9(9):e107220
references.pmid: 25233093
references.citation: Dev Biol. 2014 Oct 1;394(1):54-64
references.pmid: 25127994
references.citation: Int Immunopharmacol. 2014 Nov;23(1):236-46
references.pmid: 25196431
references.citation: J Am Soc Nephrol. 2015 May;26(5):1115-25
references.pmid: 25185988
references.citation: J Biol Chem. 2001 Oct 12;276(41):38121-38
references.pmid: 11457855
references.citation: J Biol Chem. 2002 Mar 15;277(11):8771-4
references.pmid: 11805080
references.citation: Pharmacol Rev. 2002 Sep;54(3):431-67
references.pmid: 12223531
references.citation: J Biol Chem. 2002 Oct 18;277(42):40091-8
references.pmid: 12167625
references.citation: J Intern Med. 2003 Jul;254(1):45-66
references.pmid: 12823642
references.citation: Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3645-9
references.pmid: 8475113
references.citation: J Biol Chem. 1997 Mar 7;272(10):6525-33
references.pmid: 9045678
references.citation: Oncogene. 1998 Dec 24;17(25):3237-45
references.pmid: 9916986
references.citation: J Cardiovasc Pharmacol. 2005 Jan;45(1):36-43
references.pmid: 15613977
references.citation: Diabetes. 2006 Jan;55(1):225-33
references.pmid: 16380497
references.citation: Clin Exp Pharmacol Physiol. 2006 Oct;33(10):940-5
references.pmid: 17002671
references.citation: Cell Signal. 2007 Aug;19(8):1690-700
references.pmid: 17446044
references.citation: Kidney Int. 2007 Jul;72(1):26-36
references.pmid: 17457377
references.citation: Mol Pharm. 2007 Nov-Dec;4(6):807-18
references.pmid: 17999464
references.citation: J Clin Invest. 2009 Jul;119(7):2009-18
references.pmid: 19487814
references.citation: Cell Cycle. 2010 Aug 15;9(16):3256-76
references.pmid: 20814239
references.citation: Cell Cycle. 2010 Sep 1;9(17):3515-33
references.pmid: 20855962
references.citation: J Cell Biochem. 2011 Jun;112(6):1661-72
references.pmid: 21503956
references.citation: Blood. 2011 May 12;117(19):5231-42
references.pmid: 21389321
references.citation: Cell Cycle. 2010 Jun 15;9(12):2423-33
references.pmid: 20562526
references.citation: J Clin Invest. 2011 Jun;121(6):2181-96
references.pmid: 21606597
references.citation: Cell Cycle. 2010 Jun 1;9(11):2201-19
references.pmid: 20519932
references.citation: Cell Physiol Biochem. 2011;28(2):279-88
references.pmid: 21865735
references.citation: Cell Signal. 2012 Feb;24(2):443-50
references.pmid: 21982880
references.citation: Am J Physiol Renal Physiol. 2012 Jan 1;302(1):F159-72
references.pmid: 21975875
references.citation: Clin Exp Pharmacol Physiol. 2012 Mar;39(3):283-99
references.pmid: 22118895
references.citation: Biochim Biophys Acta. 2012 Apr;1823(4):971-82
references.pmid: 22230192
references.citation: PLoS One. 2012;7(5):e36041
references.pmid: 22615747
references.citation: Cell Stress Chaperones. 2012 Jul;17(4):485-93
references.pmid: 22270613
references.citation: Planta Med. 2012 Nov;78(16):1757-60
references.pmid: 22923199
references.citation: PLoS One. 2013;8(2):e57466
references.pmid: 23460862
references.citation: Am J Physiol Renal Physiol. 2013 Mar 15;304(6):F820-30
references.pmid: 23269647
references.citation: Biochim Biophys Acta. 2013 Jun;1833(6):1434-42
references.pmid: 23499875
references.citation: PLoS One. 2014;9(2):e87871
references.pmid: 24498385
references.citation: Am J Physiol Renal Physiol. 2014 Jun 1;306(11):F1308-17
references.pmid: 24694591
references.citation: Free Radic Biol Med. 2014 Aug;73:201-13
references.pmid: 24835767
references.citation: Biomed Res Int. 2014;2014:260210
references.pmid: 25136570
references.citation: Kidney Int. 2014 Oct;86(4):666-8
references.pmid: 25265947