(Journal Article): Antioxidative treatment prevents activation of death-receptor- and mitochondrion-dependent apoptosis in the hearts of diabetic rats.
 
Bojunga J, Nowak D, Mitrou PS, Hoelzer D, Zeuzem S, Chow KU (Klinik fur Innere Medizin II, Saarland University Hospital, Kirrberger Strasse, 66421, Homburg/Saar, Germany., dr_bojunga@web.de )
 
IN: Diabetologia 2004; 47(12):2072-2080
Impact Factor(s) of Diabetologia: 5.583 (2004), 5.689 (2003), 5.136 (2002), 6.299 (2001)

Fulltext:    HTML  PDF

ABSTRACT: AIMS/HYPOTHESIS: The mechanisms by which glucose injures cells of the cardiovascular system include generation of reactive oxygen species and induction of cellular apoptosis. To date, little is known about the molecular events of hyperglycaemia-induced apoptosis in the heart in vivo. METHODS: Male Sprague-Dawley rats were rendered diabetic by a single intraperitoneal injection of 60 mg/kg body weight streptozotocin. Caspase activities in cardiac ventricular tissue were determined using fluorometric and immunoassay caspase-activity assay kits respectively. Expression levels of proteins of the apoptotic cascade were determined with western blot analyses using specific antibodies. RESULTS: Four weeks of hyperglycaemia induced significant apoptosis in cardiac tissue. Determining the initiators of death-receptor-dependent apoptosis revealed induction of CD95/Fas and caspase-8. Examination of the activities of effector caspases revealed increased activity of caspase-6, but not caspase-3 and -7. On evaluating inhibitors of apoptosis, we found up-regulation of caspase-3 and -7-inhibiting X-linked inhibitors of apoptosis in diabetic rats. Hyperglycaemia also induced significant mitochondrion-dependent apoptosis. Our evaluation of expression levels of Bcl-2 family members showed increased expression of pro-apoptotic Bak and Bax in diabetic rats. Antioxidative treatment with lipoic acid significantly suppressed apoptosis and down-regulated caspase-6, -8 and -9 activity, as well as expression levels of pro-apoptotic Bcl-2 proteins without changing blood glucose levels. CONCLUSIONS/INTERPRETATION: The present study indicates that reactive oxygen species induced by high glucose are involved in both death-receptor- and mitochondrion-dependent apoptosis in the heart in vivo. It also suggests that antioxidants may be a therapeutic option for preventing cardiovascular damage in diabetes mellitus in humans.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Mammon K, Keshet R, Savion S, Pekar O, Zaslavsky Z, Fein A, Toder V, Torchinsky A. Diabetes-Induced Fetal Growth Retardation is Associated with Suppression of NF-κB Activity in Embryos. Rev Diabetic Stud 2005. 2: 27-34.
  » Diabetes OD » Diabetic Complications » Risk of Diabetes » Diabetic Embryopathy/Fetal Gro... » Retardation » Disturbances in Protein and Ge... » NF-κB Expression » Journal Article