Generation of trans-arachidonic acid under nitrative stress is associated with upregulation of thromponsdin-1 in diabetic rats

Lin Xu, Yu Min Liu, Zhu Jun Yao, Guo Liang Xun, Wen Juan Yu, Kun Liu, Xiao Dong Sun, Yun Ping Qiu, Hai Xiang Wu, Xun Xu

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background Trans-arachidonic acids (TAAs), newly discovered markers of nitrative stress and the major products of nitrogen dioxide (NO 2 ̇)-mediated isomerization of arachidonic acid (AA), represent a new mechanism of NO 2 ̇-induced toxicity. It has been reported that TAAs were generated in oxygen-induced microvascular degeneration model and TAAs were also generated in a diabetic retinopathy (DR) model. In this study, we examined high glucose-induced nitrative stress damage and TAAs levels and explored the possible mechanisms for DR caused by reactive nitrogen species. Methods Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg. Bovine retinal capillary endothelial cells (BRECs) were selectively cultured and incubated with normal or high glucose. The serum TAAs and AA in diabetic rats were measured by the gas chromatography and mass spectrometry (GC/MS) method. The ratio of peak area of TAAs to AA with selected ion of 79 was estimated by a group t-test. Thrombospondin-1 (TSP-1) in the rat retinas and BRECs extracts were examined by Western blotting. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) protein was examined by Western blotting in BRECs incubated with high glucose. Results The TAAs to AA ratio (TAAs/AA) was significantly increased in the serum at 8, 12 and 16 weeks after STZ injection (P <0.05), with no noticeable change found at 2 or 4 weeks (P >0.05). Expression of TSP-1 in the retina of diabetic rats was progressively elevated according to the duration of diabetes. TSP-1 expression was increased in BRECs incubated with high glucose at 48 hours. Moreover, high glucose also increased ERK1/2 expression, which peaked at 30 minutes and then decreased in the following 48 hours. Conclusion An elevation of TAAs/AA is associated with high glucose-induced nitrative stress, which probably involves upregulation of TSP-1 through activating ERK1/2.

Original languageEnglish (US)
Pages (from-to)1885-1889
Number of pages5
JournalChinese medical journal
Volume124
Issue number12
DOIs
StatePublished - Jun 2011

Keywords

  • Diabetic retinopathy
  • Nitrative stress
  • Nitrogen dioxide
  • Thrombospondin-1
  • Trans-arachidonic acids

ASJC Scopus subject areas

  • Medicine(all)

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