Reduced connexin43 expression in high-grade human brain glioma cells

Astrocytes play a well-established role in brain metabolism, being a key element in the capture of energetic compounds from the circulation and in their delivery to active neurons. Their metabolic status is affected in many pathological situations, such as gliomas, which are the most common brain tumors. This proliferative dysfunction is associated with changes in gap junctional communication, a property strongly developed in normal astrocytes studied both in vitro and in vivo. Here, we summarize and discuss the findings that have lead to the identification of a link between gap junctions, glucose uptake, and proliferation. Indeed, the inhibition of gap junctional communication is associated with an increase in glucose uptake due to a rapid change in the localization of both GLUT-1 and type I hexokinase. This effect persists due to the up-regulation of GLUT-1 and type I hexokinase and to the induction of GLUT-3 and type II hexokinase. In addition, cyclins D1 and D3 have been found to act as sensors of the inhibition of gap junctions and have been proposed to play the role of mediators in the mitogenic effect observed. Conversely, in C6 glioma cells, characterized by a low level of intercellular communication, an increase in gap junctional communication reduces glucose uptake by releasing type I and type II hexokinases from the mitochondria and decreases the exacerbated rate of proliferation due to the up-regulation of the Cdk inhibitors p21 and p27. Identification of the molecular actors involved in these pathways should allow the determination of potential therapeutic targets that could lead to the testing of alternative strategies to prevent, or at least slow down, the proliferation of glioma cells.

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“…1991b), is inversely correlated with the degree of glioma malignancy (Shinoura et al . 1996; Huang et al . 1999; Soroceanu et al .…”

Section: The Inhibition Of Gap Junctional Communication Induces Astromentioning

confidence: 99%

Glucose metabolism and proliferation in glia: role of astrocytic gap junctions

Tabernero

Medina

Giaume

2006

Journal of Neurochemistry

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“…In fact, several connexins, the proteins which form gap junction channels, have been proposed as tumor suppressor proteins [4]. For instance, the expression of connexin 43, the main connexin in astrocytes [5], correlates inversely with the degree of glioma malignancy [6–8] and the transfection of connexin 43 in glioma cells decreases their rate of growth [9,10]. Therefore, the expression of connexin 43 and hence the establishment of gap junction communication decrease glioma cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Proliferation of C6 glioma cells is blunted by the increase in gap junction communication caused by tolbutamide

et al. 2001

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We have previously reported that tolbutamide prevents the inhibition of gap junction communication in astrocytes. Here, we show that tolbutamide increases gap junction communication and connexin 43 expression in poorly coupled C6 glioma cells. The increase in communication is concurrent with the inhibition of the rate of proliferation due to a block of the progression of C6 glioma cells through the S phase of the cell cycle. The effects of tolbutamide were quantitatively similar to that found after the elevation of intracellular cAMP. Furthermore, the effects of tolbutamide and cAMP were additive. The possible beneficial effect of tolbutamide on gene therapy for gliomas is discussed. ß

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“…Decreased GJIC was observed in glioblastoma (Huang et al, 1999), gastric carcinoma (Uchida et al, 1995), squamous cell carcinoma (Tada and Hashimoto, 1997) and tumors from the prostate (Tsai et al, 1996), lung (Jinn et al, 1998), liver (Krutovskikh et al, 1994), ovary (Hanna et al, 1997), colon (Friedman and Steinberg, 1982), and breast (Locke, 1998), as well as many chemically and virally transformed cells (Hanna et al, 1997; Cesen‐Cummings et al, 1998). Furthermore, endogenously expressed connexins decreased the transformed phenotype of cell lines derived from hepatoma (Eghbali et al, 1991), mammary carcinoma (Hirschi et al, 1996), glioma (Huang et al, 1999), and melanoma (Su et al, 2000). In UACC903 melanoma cells, overexpression of Cx43 (connexin 43) was shown to suppress anchorage‐independent growth and tumor formation in nude mice (Su et al, 2000).…”

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confidence: 99%

The impact of human immunodeficiency virus infection in liver transplantation for hepatocellular carcinoma

et al. 2011

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We read with interest the reviews by Ghouri et al. 1 and Martinez et al. 2 Ghouri et al. analyzed the association of nonalcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD) and concluded that although a diagnosis of NAFLD should prompt diabetes screening, it is insufficient for considering patients to be at high risk for CVD. Martinez et al. evaluated noninvasive methods for assessing liver fibrosis and recommended that those tests with the highest diagnostic accuracy be validated against liver biopsy to facilitate their implementation in clinical practice.We meta-analyzed prospective data regarding the natural history of NAFLD and studies assessing the diagnostic accuracy of noninvasive methods for liver disease severity against liver biopsy in NAFLD, and we reached the following conclusions 3 :1. The two NAFLD histological subtypes, simple steatosis (SS) and nonalcoholic steatohepatitis (NASH), have different risks of liver-related complications: SS progresses to cirrhosis in less than 5% of cases; NASH progresses to cirrhosis in 10% to 15% of cases over 10 years and in 25% to 30% of cases in the presence of advanced fibrosis. 2. NAFLD patients have a 1.44-to 2.05-fold higher rate of CVD (depending on whether the diagnosis is based on an aminotransferase elevation or radiological/histological criteria) than the general population; restricting the analysis to studies adjusting for metabolic syndrome did not change the risk. Importantly, CVD mortality did not differ among NAFLD histological subtypes. ; restricting the analysis to studies adjusting for metabolic syndrome did not change the risk. Whether the risk of diabetes differs among NAFLD histological subtypes remains unclear: in a communitybased study, the 13-year incidence of diabetes was 2.98-fold higher in NASH patients versus SS patients. 3According to our analysis, a diagnosis of NAFLD should prompt a thorough three-focus assessment of cardiovascular, metabolic, and liver-related risks (Table 1). 4 Liver-related risk assessment remains problematic because it requires liver histology. Three noninvasive methods have been extensively validated: enzyme-linked immunosorbent assay-detected cytokeratin 18 fragments (9 studies enrolling 856 participants) for the detection of NASH and the NAFLD fibrosis score (13 studies enrolling 3064 participants) and FibroScan (6 studies enrolling 563 participants) for the detection of advanced fibrosis. We believe that these methods should be promptly implemented in diagnostic algorithms to select patients for liver biopsy in routine clinical practice while we continue to search for the ideal noninvasive marker.

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Reduced connexin43 expression in high-grade human brain glioma cells

Cited by 24 publications

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Glucose metabolism and proliferation in glia: role of astrocytic gap junctions

Glucose metabolism and proliferation in glia: role of astrocytic gap junctions

Proliferation of C6 glioma cells is blunted by the increase in gap junction communication caused by tolbutamide

The impact of human immunodeficiency virus infection in liver transplantation for hepatocellular carcinoma

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