| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on June 1, 2006
Accepted on August 16, 2006
Department of Experimental Medicine and Oncology, General Pathology Section, Corso Raffaello 30, 10125 Turin; Department of Clinical Pathophysiology, Via Genova 3, 10126 Turin; Department of Analytical Chemistry, Via Pietro Giuria 5, 10125 Turin -University of Turin, ITALY
* To whom correspondence should be addressed. E-mail: giuseppe.boccuzzi{at}unito.it.
Oxidative stress plays a key role in the pathogenesis of diabetic cardiomyopathy, which is characterized by myocyte loss and fibrosis, finally resulting in heart failure. The study looks at the downstream signaling whereby oxidative stress leads to reduced myocardial contractility in the left ventricle of diabetic rats and at the effects of dehydroepiandrosterone (DHEA), which production is suppressed in the failing heart and which prevents the oxidative damage induced by hyperglycemia in several experimental models.
DHEA was given orally at a dose of 4 mg/rat/day for 21 days to rats with streptozotocin-induced diabetes and to genetic diabetic-fatty rats (ZDF). Oxidative balance, AGE (advanced glycated end products) and AGE receptors, cardiac myogenic factors and myosin heavy chain genes expression were determined in the left ventricle of treated and untreated STZ-diabetic rats and ZDF-rats.
Oxidative stress induced by chronic hyperglycemia increases AGE and AGE-receptors, and led to activation of the pleoitropic transcription factor NFkB. NFkB activation triggered a cascade of signaling which finally led to the switch in the cardiac myosin heavy chain (MHC) gene expression from the 
-MHC isoform to the 
-MHC isoform. DHEA treatment, by preventing the activation of the oxidative pathways induced by hyperglycemia, counteracted the enhanced AGE-receptor activation in the heart of STZ-diabetic rats and of ZDF-rats, and normalized down-stream signaling, thus avoiding impairment of the cardiac myogenic factors, heart autonomic nervous system and neural crest derivatives (HAND) and myogenic enhancer factor-2 (MEF-2), and the switch in MHC gene expression, which are the early events in diabetic cardiomyopathy.
This article has been cited by other articles:
 |
|
 |
|
  M. Aragno, R. Mastrocola, G. Alloatti, I. Vercellinatto, P. Bardini, S. Geuna, M. G. Catalano, O. Danni, and G. Boccuzzi Oxidative Stress Triggers Cardiac Fibrosis in the Heart of Diabetic Rats Endocrinology, January 1, 2008; 149(1): 380 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Hydock, C.-Y. Lien, C. M. Schneider, and R. Hayward Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3254 - H3264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Brignardello, C. Runzo, M. Aragno, M. G. Catalano, M. Cassader, P. C. Perin, and G. Boccuzzi Dehydroepiandrosterone Administration Counteracts Oxidative Imbalance and Advanced Glycation End Product Formation in Type 2 Diabetic Patients Diabetes Care, November 1, 2007; 30(11): 2922 - 2927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Marinelli, E. Trevisi, L. Da Dalt, M. Merlo, G. Bertoni, and G. Gabai Dehydroepiandrosterone secretion in dairy cattle is episodic and unaffected by ACTH stimulation J. Endocrinol., September 1, 2007; 194(3): 627 - 635. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
