Evaluation of Bcl‐2 Expression and Caspase‐3 in STZ‐Induced Diabetic Rats

Abstract

We assessed the expression of Bcl-2 family members at both mRNA and protein levels as well as the Caspase-3 activity, in order to investigate the occurrence of apoptosis in hippocampus of STZ-induced diabetic rats. We selected twenty-four Wistar rats; half of them were made diabetic by intraperitoneal injection of a single 60 mg/kg dose of streptozotocin (STZ, IP), while the others received normal saline and served as controls. The expressions of Bcl-2, Bcl-xL, and Bax mRNA and proteins were measured using RT-PCR and western blotting, respectively. Caspases-3 activity was determined by using the Caspase-3/CPP32 Fluorometric Assay Kit. The result showed that mRNA and protein levels of Bcl-2 and Bcl-xL were lower in hippocampus of diabetic group than that of the control group, whereas expressions of Bax in hippocampus of diabetic rats were higher than that of controls at both mRNA and protein levels (P < .01). Hyperglycemia was found to raise 6.9-fold hippocampal caspase-3 activity in diabetic group compared with control group (P < .001). Therefore, the induction of diabetes is associated with increased ratios of Bax/Bcl-2, Bax/Bcl-xL, and increased caspase-3 activity in hippocampus which shows that apoptosis is favored in hippocampal region.

The Biologic Potential of Lyophilized Extracts of Brickellia cavanillesii (Asteraceae): Apoptosis and Glut 2 Gene Expression

“…Other studies on PC12 cells indicated that apoptosis was induced when excess concentration of glucose led to an increase in Bax expression [52]. Investigations by Anarkooli et al revealed the activation of proapoptotic proteins and suppression of antiapoptotic proteins in hippocampus of STZ-induced diabetic rats at both mRNA and protein levels using Bax/ Bcl-xl ratios [43]. An analysis of the genes that were significantly regulated by LBC indicates that while several antiapoptotic genes were significantly up-regulated, some apoptotic genes were also significantly down-regulated.…”

“…CARD8 is involved in pathways leading to the activation of caspases or nuclear factor kappa-B. Caspase enzymes play an effective role in apoptosis of neurons of central nervous system [43]. CASP1 belongs to the cysteine proteases family (caspases).…”

“…The two groups of this family, Bcl-2 and Bax are diametrically opposed; Bcl-2 and Bcl-xl act to inhibit apoptosis while Bax activates apoptosis. Other studies have employed Bax/Bcl-2 and Bax/Bcl-xl ratios as the key index of apoptotic cell death [43]. Studies suggest that over expression of Bax can induce apoptosis in cells both in vivo and in vitro [50,51].…”

Adenosine monophosphate-activated protein kinase activation mediates the leptin-induced attenuation of cognitive impairment in a streptozotocin-induced rat model

“…Jafari Anarkooli et al (9) demonstrated that Bcl-2 family gene expression and caspase-3 activity were altered in the streptozotocin (STZ)-induced diabetic rat hippocampus. Furthermore, Revsin et al (10) found that a glucocorticoid receptor antagonist normalized hippocampal alterations and cognitive impairment in STZ-induced diabetic mice.…”

Diabetic encephalopathy: the role of oxidative stress and inflammation in type 2 diabetes

“…89,80 Therefore, it is plausible to admit that neurodegenerative diseases and diabetic encephalopathy have a genetic and biochemical common ground. 4 Alzheimer's disease -type 3 diabetes AD is a neurological disorder characterized by profound memory loss and progressive cognitive and behavioral decline due to selective loss or dysfunction of neurons in specific brain regions/neural circuits, including the neocortex, hippocampus, and basal forebrain.…”