5-lipoxygenase expression and activity in aorta from streptozotocin-induced diabetic rats

Prostaglandins Other Lipid Mediat. 2005 Jan;75(1-4):91-103. doi: 10.1016/j.prostaglandins.2004.10.002.

Abstract

We previously reported an activation of the 5-lipoxygenase pathway in aorta from streptozotocin-induced diabetic rats. The aim of this study was to investigate whether this activation was associated with an increased expression of 5-lipoxygenase, an increased cysteinyl leukotriene (CysLT) production in response to arachidonic acid or calcium ionophore A23187 and/or a hypersensitivity of the aorta to CysLTs in streptozotocin-induced diabetic rats. In aorta from diabetic and control rats, reverse transcriptase-PCR and western blot analysis with a specific 5-lipoxygenase antibody provided evidence for the presence of 5-lipoxygenase in aorta. However, the expression of 5-lipoxygenase was not significantly different between diabetic and control rats. Challenge by A23187 (10 microM) and arachidonic acid (10 microM and 0.1 mM) with or without A23187 (10 micromol/l) induced a significant increase of CysLT release (measured by enzyme immunoassay) that was in the same range in aorta from control and diabetic rats. In contrast, aortas from diabetic rats showed a greater sensitivity to LTC4 and LTD4 contractile effects. These data suggested that the activation of the 5-lipoxygenase pathway previously reported in streptozotocin-induced diabetic rats could be explained by an augmented sensitivity to CysLTs of the diabetic aorta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / enzymology*
  • Aorta, Thoracic / physiopathology
  • Arachidonate 5-Lipoxygenase / genetics*
  • Arachidonate 5-Lipoxygenase / metabolism
  • Arachidonic Acid / pharmacology
  • Calcimycin / pharmacology
  • DNA Primers
  • Diabetes Mellitus, Experimental / enzymology*
  • Gene Expression Regulation, Enzymologic*
  • In Vitro Techniques
  • Isometric Contraction
  • Leukotrienes / pharmacology*
  • Male
  • Muscle Tonus / drug effects
  • Muscle, Smooth, Vascular / enzymology
  • Muscle, Smooth, Vascular / physiopathology
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA Primers
  • Leukotrienes
  • Arachidonic Acid
  • Calcimycin
  • Arachidonate 5-Lipoxygenase