TITLE:
Downregulation of Nrf2 and HO-1 expression contributes to oxidative stress in type 2 diabetes mellitus: A study in Juana Koslay City, San Luis, Argentina
AUTHORS:
Susana Siewert, Irma González, Lucas Santillán, Roberto Lucero, Marta S. Ojeda, María S. Gimenez
KEYWORDS:
Type 2 Diabetes Mellitus; HO-1; Nrf2 and TBAR’S
JOURNAL NAME:
Journal of Diabetes Mellitus,
Vol.3 No.2,
May
15,
2013
ABSTRACT: Oxidative
stress is associated with diabetes mellitus, a condition characterized by increased
prevalence and progression rate of cardiovascular disease. NFE2-related factor
2 (Nrf2) is a master regulator of cellular detoxification responses and redox
status. The aim of this study was to examine associations between type 2
Diabetes Mellitus (T2DM), oxidative stress and the expression of NFE2-related
factor 2 (Nrf2) in a population of diabetic patients living in Juana Koslay
City, San Luis, Argentina. In addition, we evaluated the functional relevance
of Nrf2 by measuring the HO-1 expression among persons with type 2 diabetes. We
measured clinical and biochemical parameters related to lipid metabolism and
oxidative stress in a population of Type 2 Diabetes Mellitus patients (T2DM, n =
40) and controls (Co, n = 30). Compared to Co, T2DM patients had higher fasting
serum glucose, glycated hemoglobin, triglycerides, total cholesterol,
low-density lipoprotein cholesterol, and thiobarbituric acid reactive
substances and lower high-density
lipoprotein cholesterol. T2DM individuals had also higher atherogenic
index and body mass index than controls. We also founded that HO-1 mRNA in
whole blood was lower in T2DM than controls, suggesting that T2DM may have an
altered antioxidant response to oxidative stress. Interestingly, we found reduced
Nrf2 mRNA in whole blood from T2DM compared to Co. The results from this study
provide novel evidence that genes associated to antioxidant defense mechanisms
are markedly reduced in patients with type 2 diabetes, and that the reduction
in the expression of these genes could be associated to hyperglycemia and
increased levels of MDA. Linear regression analysis revealed that there was a
strong and positive correlation between the changes of Nrf2 and HO-1 expression
levels.