Succination of thiol groups in adipose tissue proteins in diabetes. Succination inhibits polymerization and secretion of adiponectin

Norma Frizzell, Mathur Rajesh, Matthew J. Jepson, Ryoji Nagai, James Carson, Suzanne R. Thorpe, John W. Baynes

Research output: Contribution to journalArticle

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Abstract

S-(2-Succinyl) cysteine (2SC) is formed by reaction of the Krebs cycle intermediate fumarate with cysteine residues in protein, a process termed succination of protein. Both fumarate and succination of proteins are increased in adipocytes cultured in high glucose medium (Nagai, R., Brock, J. W., Blatnik, M., Baatz, J. E., Bethard, J., Walla, M. D., Thorpe, S. R., Baynes, J. W., and Frizzell, N. (2007) J. Biol. Chem. 282, 34219-34228). We show here that succination of protein is also increased in epididymal, mesenteric, and subcutaneous adipose tissue of diabetic (db/db) mice and that adiponectin is a major target for succination in both adipocytes and adipose tissue. Cys-39, which is involved in cross-linking of adiponectin monomers to form trimers, was identified as a key site of succination of adiponectin in adipocytes. 2SC was detected on two of seven monomeric forms of adiponectin immunoprecipitated from adipocytes and epididymal adipose tissue. Based on densitometry, 2SC-adiponectin accounted for ∼7 and 8% of total intracellular adiponectin in cells and tissue, respectively. 2SC was found only in the intracellular, monomeric forms of adiponectin and was not detectable in polymeric forms of adiponectin in cell culture medium or plasma. We conclude that succination of adiponectin blocks its incorporation into trimeric and higher molecular weight, secreted forms of adiponectin. We propose that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes.

Original languageEnglish (US)
Pages (from-to)25772-25781
Number of pages10
JournalJournal of Biological Chemistry
Volume284
Issue number38
DOIs
StatePublished - Sep 18 2009

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Adiponectin
Medical problems
Sulfhydryl Compounds
Polymerization
Adipose Tissue
Tissue
Proteins
Adipocytes
Fumarates
Citric Acid Cycle
Plasmas
Densitometry
Subcutaneous Fat
Biomarkers
Cell culture
Cysteine
Culture Media
Cell Culture Techniques
Monomers
Molecular Weight

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Succination of thiol groups in adipose tissue proteins in diabetes. Succination inhibits polymerization and secretion of adiponectin. / Frizzell, Norma; Rajesh, Mathur; Jepson, Matthew J.; Nagai, Ryoji; Carson, James; Thorpe, Suzanne R.; Baynes, John W.

In: Journal of Biological Chemistry, Vol. 284, No. 38, 18.09.2009, p. 25772-25781.

Research output: Contribution to journalArticle

Frizzell, Norma ; Rajesh, Mathur ; Jepson, Matthew J. ; Nagai, Ryoji ; Carson, James ; Thorpe, Suzanne R. ; Baynes, John W. / Succination of thiol groups in adipose tissue proteins in diabetes. Succination inhibits polymerization and secretion of adiponectin. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 38. pp. 25772-25781.
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AU - Carson, James

AU - Thorpe, Suzanne R.

AU - Baynes, John W.

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