Diabetes increases p53-mediated apoptosis following ischemia.

Abstract:

BACKGROUND:Diabetes impairs the ability of tissue to respond adequately to ischemia. The underlying mechanisms contributing to this impaired response remain unknown. Because increases in apoptosis have been linked to a spectrum of diabetic complications, the authors examined whether programmed cell death is involved in the pathogenesis of poor diabetic tissue responses to ischemia. METHODS:Analysis for apoptosis and levels of proaptotic protein, p53, were performed on streptozocin-induced diabetic mice and wild-type controls in a murine model of soft-tissue ischemia (n = 6). In vitro, chronic hyperglycemic culture conditions were used to test inducibility and reversibility of the diabetic phenotype. Small interfering RNA was used to assess the role of p53. RESULTS:Ischemia-induced apoptosis and p53 levels were increased significantly in diabetic dermal fibroblasts both in vivo and in vitro. Chronic hyperglycemic culture was sufficient to induce the increased apoptotic phenotype, and this was not reversible with long-term normoglycemic conditions. Blocking p53 with small interfering RNA resulted in significant protection against ischemic apoptosis. CONCLUSIONS:These findings suggest that diabetes causes an increased apoptotic response to ischemia through a p53-mediated mechanism. This increase is not reversible by exposure to low-glucose conditions. This suggests that glycemic control alone will be unable to prevent tissue necrosis in diabetic patients and suggests novel therapeutic strategies for this condition.

journal_name

Plast Reconstr Surg

authors

Jazayeri L,Callaghan MJ,Grogan RH,Hamou CD,Thanik V,Ingraham CR,Capell BC,Pelo CR,Gurtner GC

doi

10.1097/01.prs.0000302499.18738.c2

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

1135-1143

issue

4

eissn

0032-1052

issn

1529-4242

pii

00006534-200804000-00009

journal_volume

121

pub_type

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