Relationship between reduced BCL-2 expression in circulating mononuclear cells and early nephropathy in type 1 diabetes.
Int J Immunopathol Pharmacol
; 18(4): 625-35, 2005.
Article
en En
| MEDLINE
| ID: mdl-16388709
ABSTRACT
Microalbuminuria is the earliest clinical evidence of diabetic nephropathy, but the mechanisms linking hyperglycemia and kidney complications are not clear. The aim of this study was to evaluate whether enhanced oxidative stress in patients with microalbuminuria can contribute to diabetic nephropathy development through downregulation of the antiapoptotic gene Bcl-2 that promotes in turn a pro-inflammatory status. We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared to 15 matched healthy controls. Plasma oxidant status, and expression of Bcl-2, activated NF-kB, inducible Nitric Oxide synthase (iNOS), and monocyte chemoattractant protein (MCP)-1 in circulating monocytes were evaluated at baseline and after 8-week oral vitamin E treatment (600 mg b.i.d.). Bcl-2 expression was significantly reduced in microalbuminuric diabetic patients as a consequence of increased oxidant burden secondary to persistent hyperglycemia. Bcl-2 down-regulation was associated with enhanced expression of NF-kB, iNOS and MCP-1, and showed a strong correlation with the albumin excretion rate. Low Bcl-2 expression and high inflammatory status were normalized by vitamin E both in vivo and in vitro. Our study showed that Bcl-2 down-regulation in diabetic patients with poor glycemic control results in the activation of the NF-kB pathway leading to the development of nephropathy. Vitamin E might provide a novel form of therapy for prevention of nephropathy in diabetic patients in which an acceptable glycemic control is difficult to achieve despite insulin therapy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Monocitos
/
Expresión Génica
/
Genes bcl-2
/
Diabetes Mellitus Tipo 1
/
Nefropatías Diabéticas
Límite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Int J Immunopathol Pharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
PATOLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Italia