title: Role of redox environment on the oligomerization of higher molecular weight adiponectin.
abstract: BACKGROUND
  Adiponectin is an adipocyte-secreted hormone with insulin-sensitizing and anti-inflammatory actions. The assembly of trimeric, hexameric, and higher molecular weight (HMW) species of adiponectin is a topic of significant interest because physiological actions of adiponectin are oligomer-specific. In addition, adiponectin assembly is an example of oxidative oligomerization of multi-subunit protein complexes in endoplasmic reticulum (ER).
  
  
  RESULTS
  We previously reported that trimers assemble into HMW adiponectin via intermediates stabilized by disulfide bonds, and complete oxidation of available cysteines locks adiponectin in hexameric conformation. In this study, we examined the effects of redox environment on the rate of oligomer formation and the distribution of oligomers. Reassembly of adiponectin under oxidizing conditions accelerated disulfide bonding but favored formation of hexamers over the HMW species. Increased ratios of HMW to hexameric adiponectin could be achieved rapidly under oxidizing conditions by promoting disulfide rearrangement.
  
  
  CONCLUSIONS
  Based upon these observations, we propose oxidative assembly of multi-subunit adiponectin complexes in a defined and stable redox environment is favored under oxidizing conditions coupled with high rates of disulfide rearrangement.
authors: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85724, USA.
authors: David B
authors: DB
authors: Briggs
authors: Rebecca M
authors: RM
authors: Giron
authors: Pamela R
authors: PR
authors: Malinowski
authors: Martha
authors: M
authors: Nuñez
authors: Tsu-Shuen
authors: TS
authors: Tsao
references: Int J Obes (Lond). 2008 Dec;32 Suppl 7:S13-8
references: 19136982
references: Proteins. 1995 Mar;21(3):167-95
references: 7784423
references: Endocrinology. 2008 May;149(5):2270-82
references: 18202126
references: J Biol Chem. 2004 Mar 26;279(13):12152-62
references: 14699128
references: Curr Biol. 1998 Mar 12;8(6):335-8
references: 9512423
references: J Biol Chem. 1997 Dec 5;272(49):30780-6
references: 9388218
references: Arch Biochem Biophys. 1998 Oct 1;358(1):25-39
references: 9750161
references: Annu Rev Biophys. 2008;37:289-316
references: 18573083
references: Science. 2004 Oct 15;306(5695):457-61
references: 15486293
references: Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E421-7
references: 17488807
references: Trends Cardiovasc Med. 2006 Jul;16(5):141-6
references: 16781946
references: Mol Cell Biol. 2007 May;27(10):3716-31
references: 17353260
references: Diabetes Care. 2006 Jun;29(6):1357-62
references: 16732021
references: Nat Clin Pract Cardiovasc Med. 2009 Jan;6(1):27-35
references: 19029992
references: Eur J Endocrinol. 2005 Sep;153(3):409-17
references: 16131604
references: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18302-7
references: 19011089
references: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18077-8
references: 19020096
references: Science. 1992 Sep 11;257(5076):1496-502
references: 1523409
references: J Biol Chem. 2003 Mar 14;278(11):9073-85
references: 12496257
references: Diabetes Obes Metab. 2006 May;8(3):264-80
references: 16634986
references: Cell. 2008 Nov 28;135(5):933-47
references: 19026441
references: Obesity (Silver Spring). 2007 May;15(5):1172-8
references: 17495193
references: J Biol Chem. 2003 Oct 10;278(41):40352-63
references: 12878598
references: FEBS Lett. 2007 Mar 6;581(5):809-14
references: 17292892
references: Diabetes. 2010 Nov;59(11):2949-59
references: 20802255
references: Biochemistry. 2009 Dec 29;48(51):12345-57
references: 19943704
references: Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):29-33
references: 14551151
references: Mol Cell Biol. 2007 Jul;27(13):4698-707
references: 17452443
references: Biochem J. 2009 Dec 14;425(1):41-52
references: 20001961
references: J Biol Chem. 2003 Dec 12;278(50):50810-7
references: 14522956
references: Diabetes. 2006 Jul;55(7):1954-60
references: 16804063
references: J Biol Chem. 2002 Aug 16;277(33):29359-62
references: 12087086
references: Am J Physiol Endocrinol Metab. 2006 Jan;290(1):E42-E46
references: 16118250