Possible Relation of Hemin-Induced HO-1 Expression to the Upregulation of VEGF and BDNF mRNA Levels in Rat C6 Glioma Cells

Abstract

Glial cells are generally considered to contribute to retaining the integrity of neural function through the protection of neuronal cells against neurodegenerative insults and also expected to play a potential role in the protection of cerebrovascular systems from various toxic insults of hemorrhaged blood, thus proposing a possible implication of glial cells in the recovery of brain function from the damage caused by cerebral hemorrhage. Based on this hypothetical idea, the direct effect of hemin on the expression of genes encoding heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) in glial cells was examined using rat C6 glioma cells as an in vitro model system. Hemin elevated both HO-1 and VEGF mRNA levels in the glioma cells at the concentration causing no critical damage to the cells, and the elevation of BDNF mRNA levels was also observed by exposing the cells to hemin under the same conditions. Furthermore, the elevation of VEGF and BDNF mRNA levels induced by hemin was blocked by pretreatment of the cells with the agents inhibiting not only HO-1 gene expression but also its enzymatic activity. These pharmacological studies indicate that hemin can induce the enhancement of VEGF and BDNF gene expression probably through the mechanism mediated by HO-1 activity in the glioma cells, proposing the possibility that glial cells are capable of contributing to the recovery of brain function from the damage caused by cerebral hemorrhage through the production of neurogenic and angiogenic factors.

Minocycline-Preconditioned Neural Stem Cells Enhance Neuroprotection after Ischemic Stroke in Rats

“…Activation of Nrf2 stimulates transcription of ATF4, which in turn directly transactivates the VEGF gene in endothelial cells (Afonyushkin et al, 2010, 2011). In addition, HO-1, whose expression level was regulated by Nrf2 in the present study, mediates the synthesis of VEGF in various cell types (Dulak et al, 2008), as well as BDNF and GDNF in astrocytes and neurons (Morita et al, 2009; Hung et al, 2010). These studies suggest that minocycline-induced overexpression of Nrf2 and subsequent up-regulation of HO-1 lead to increased paracrine factor expression.…”

Brain-derived neurotrophic factor regulates cell motility in human colon cancer

“…In this sense, the need for studying the prognostic significance of HO-1 in colon cancer is urgent. Results of several studies have indicated that neurotrophic factor-enhanced HO-1 expression promotes cancer cell proliferation (Morita et al 2009). In our previous study and the present report, we investigated the molecular mechanism of HO-1 and its role in cancer cell motility .…”

Evaluation of Eight Plasma Proteins as Candidate Blood-Based Biomarkers for Malignant Gliomas

“…Candidate proteins were selected based on prior studies on brain injury, or BBB disruption that suggested that these markers are brain specific, and based on availability of the respective assays for detection in our laboratory (10, 24, 30, 46, 47, 55). The goal of this study was to determine whether there are differences in plasma concentrations of these markers between patients with malignant gliomas and those without and to assess whether our findings would warrant further investigation of these markers as potential biomarkers for gliomas.…”