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Involvement of glycation and oxidative stress in diabetic macroangiopathy

N Taniguchi1, H Kaneto, M Asahi

  • 1Department of Biochemistry, Osaka University Medical School, Japan.

Diabetes
|July 1, 1996
PubMed

Insights

Diabetic conditions increase oxidative stress via the Maillard reaction, impairing antioxidant enzymes. This oxidative stress promotes smooth muscle cell proliferation and diabetic macroangiopathy by enhancing gene expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF).

Area of Science:

  • Biochemistry and Molecular Biology
  • Diabetic Complications Research
  • Cardiovascular Pathogenesis

Background:

  • Diabetic conditions exacerbate oxidative stress through the Maillard reaction, decreasing antioxidant enzyme activity (e.g., Cu,Zn-superoxide dismutase).
  • Oxidative stress damages cellular components and contributes to diabetic complications, notably macroangiopathy.
  • Smooth muscle cell (SMC) proliferation, driven by growth factors like platelet-derived growth factor (PDGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), is implicated in macroangiopathy progression.

Purpose of the Study:

  • To investigate the role of glycation reactions and oxidative stress in the pathogenesis of diabetic macroangiopathy.
  • To elucidate the specific mechanisms by which 3-deoxyglucosone (3-DG) influences gene expression of growth factors involved in SMC proliferation.

Main Methods:

  • Analysis of the Maillard reaction's impact on reactive oxygen species (ROS) production and antioxidant enzyme activity in diabetic conditions.
  • Assessment of oxidative stress markers and their correlation with DNA, lipid, and protein damage.
  • Investigation of growth factor production by SMCs, focusing on PDGF and HB-EGF.
  • Examination of the transcriptional regulation of HB-EGF by 3-DG and the role of ROS in this induction.

Main Results:

  • Diabetic conditions lead to increased oxidative stress and reduced antioxidant enzyme activity.
  • Oxidative stress is linked to cellular damage and the progression of macroangiopathy.
  • HB-EGF, a potent mitogen for SMCs, is transcriptionally regulated by 3-DG, a key glycation intermediate.
  • The induction of HB-EGF by 3-DG appears to be mediated by ROS generated from 3-DG.

Conclusions:

  • Glycation reactions, particularly involving 3-DG, significantly contribute to diabetic macroangiopathy pathogenesis.
  • Enhanced gene expression of HB-EGF, triggered by 3-DG-induced oxidative stress, plays a crucial role in SMC proliferation and macroangiopathy progression in diabetes.

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