Pharmacological Modulation of Heat Shock Protein 70 (HSP70)—Dependent Mechanisms of Endogenous Neuroprotection in Conditions of Prenatal Chronic Alcoholism by Cerebrocurin and Tiocetam

Abstract

Objective:One of the primary reactions of the genome in response to stress is different genesis induction of heat shock proteins -HSP. The purpose of this study was to investigate the concentration of heat shock protein (HSP70) and hypoxia-inducible factor (HIF-1) in the brain of rats undergoing chronic prenatal alcoholism in different periods of ischemia and define the role of these proteins in the implementation of neuroprotective effect of Cerebrocurin and Tiocetam.

Role of HIF-1α in Alcohol-Mediated Multiple Organ Dysfunction

“…Since both insulin and IGF-1 have been shown in other models to stabilize HIF-1α in mouse preadipocytic cells and in human retinal epithelial cells [22,35], diminished insulin and IGF following prenatal alcohol exposure may attribute to the downregulation of HIF-1α seen in the brain by similar mechanisms. Similar to prenatal alcohol exposure [33,34], chronic binge alcohol exposure decreased HIF-1α expression [36]. Interestingly, this study also demonstrated reductions in the insulin/IGF-1-regulated gene aspartyl–asparaginyl–β-hydroxylase.…”

“…Prenatal alcohol exposure is associated with teratogenesis, including deficient development of motor skills and developmental growth derangements [32,33], as evidenced by reduced heart, limb, and brain development [32]. Chronic prenatal alcohol exposure in rats significantly reduced HIF-1α levels [33,34], which is likely due to the decreased expression of HIF-1α stabilization proteins, such as heat shock protein (HSP)-70 [34]. Tong et al investigated the role of prenatal exposure of ethanol on juvenile rats, which impaired the insulin/insulin-like growth factor (IGF) pathway [33].…”

“…Pharmacological treatments have also been utilized to improve alcohol-induced pathologies. In conditions in which diminished HIF-1α levels are associated with damage, e.g., brain [34], prenatal exposure to ethanol and intraperitoneal treatment with tiocetam (125 mg/kg) and cerebrocurin (0.06 mg/kg) increased HIF-1α and HSP-70 levels and was neuroprotective against alcoholic encephalopathy [34]. Similarly, prenatal exposure and treatment with emodin increased HIF-1α, improved embryo development, and increased the levels of antioxidants SOD1 and SOD2 while decreasing inflammation (TNF-α) and apoptosis as measured by caspase 3 levels [32].…”

“…HIF-1 regulates hundreds of genes [27,28]; therefore, altered expression, whether an increased or decreased expression of the stabilized subunit HIF-1α, could have widespread effects on gene expression of its targets. For example, in instances in which ethanol reduced the expression of HIF-1α [32,34], agents which elevated HIF-1α aided in alleviating alcohol-mediated adverse effects, whereas in circumstances in which alcohol-induced HIF-1α expression, the use of treatments that knocked down HIF-1α improved outcomes associated with alcohol exposure. Therefore, understanding the HIF-1α needs of the organ following alcohol exposure is required to develop the appropriate therapeutic interventions.…”