Cocoa polyphenols attenuate hydrogen peroxide-induced inhibition of gap-junction intercellular communication by blocking phosphorylation of connexin 43 via the MEK/ERK signaling pathway☆

Lee, Dong‐Eun; Kang, Nam Joo; Lee, Kyung Mi; Lee, Bo Kyung; Lee, Ki Won; Lee, Hyong Joo

doi:10.1016/j.jnutbio.2009.03.014

Cited by 22 publications

(17 citation statements)

References 33 publications

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“…In contrast to the effect on hemichannels, H 2 O 2 caused uncoupling of gap junctions in cultured cortical astrocytes. This is in agreement with various studies done in epithelial cells and other cell types (20,23,(57)(58)(59)(60)(61) but inconsistent with the finding from rat striatum astrocytes (35). These authors pointed out that H 2 O 2 -induced increase in GJIC in astrocytes is very atypical as endogenous GJIC is typically high in astrocytes (35).…”

Section: Discussionsupporting

confidence: 70%

Gap Junction Intercellular Communication Mediated by Connexin43 in Astrocytes Is Essential for Their Resistance to Oxidative Stress

Sin

Lozinsky

et al. 2014

Journal of Biological Chemistry

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Oxidative stress induced by reactive oxygen species (ROS) is associated with various neurological disorders including aging, neurodegenerative diseases, as well as traumatic and ischemic insults. Astrocytes have an important role in the anti-oxidative defense in the brain. The gap junction protein connexin43 (Cx43) forms intercellular channels as well as hemichannels in astrocytes. In the present study, we investigated the contribution of Cx43 to astrocytic death induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which Cx43 exerts its effects. Lack of Cx43 expression or blockage of Cx43 channels resulted in increased ROS-induced astrocytic death, supporting a cell protective effect of functional Cx43 channels. H2O2 transiently increased hemichannel activity, but reduced gap junction intercellular communication (GJIC). GJIC in wild-type astrocytes recovered after 7 h, but was absent in Cx43 knock-out astrocytes. Blockage of Cx43 hemichannels incompletely inhibited H2O2-induced hemichannel activity, indicating the presence of other hemichannel proteins. Panx1, which is predicted to be a major hemichannel contributor in astrocytes, did not appear to have any cell protective effect from H2O2 insults. Our data suggest that GJIC is important for Cx43-mediated ROS resistance. In contrast to hypoxia/reoxygenation, H2O2 treatment decreased the ratio of the hypophosphorylated isoform to total Cx43 level. Cx43 has been reported to promote astrocytic death induced by hypoxia/reoxygenation. We therefore speculate the increase in Cx43 dephosphorylation may account for the facilitation of astrocytic death. Our findings suggest that the role of Cx43 in response to cellular stress is dependent on the activation of signaling pathways leading to alteration of Cx43 phosphorylation states.

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Section: Discussionsupporting

confidence: 70%

Gap Junction Intercellular Communication Mediated by Connexin43 in Astrocytes Is Essential for Their Resistance to Oxidative Stress

Sin

Lozinsky

et al. 2014

Journal of Biological Chemistry

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“…These results are in accordance with previous data reporting that cocoa polyphenol blocked H 2 O 2 -induced phosphorylation of Cx43 through MAPKs signaling, thereby protecting GJIC (32). Furthermore, our data confirmed that FPM scavenged ABTS free radicals and attenuated the ROS generation and lipid peroxidation.…”

Section: Antioxidant Capacity Of Fpm In Hepg2 Cellssupporting

confidence: 93%

“…Relative density was determined using a densitometry image analysis program. *p<0.05, **p<0.01, and ***p<0.001 compared with control group treated with H 2 O 2 alone induced by ROS(31,32). Givens that FPM exhibited antioxidant activity, therefore, we investigated whether FPM recovers H 2 O 2 -induced inhibition of GJIC in WB-F344 cells.The effects of FPM on the inhibition of GJIC in WB-F344 cells are shown in…”

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confidence: 97%

Antioxidant activity of Fragilariopsis pseudonana and protective effect against hydrogen peroxide-induced inhibition of gap junctional intercellular communication

Kang

Ahn

et al. 2012

Food Sci Biotechnol

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This study was aimed to evaluate antioxidant activities of a methanol extract from the polar microalgae Fragilariopsis pseudonana (FP) and to investigate the protective effect for gap junctional intercellular communication (GJIC) in WB-F344 normal rat liver epithelial cells. The results indicated that the methanol extract of FP (FPM) scavenged ABTS free radicals and inhibited copper-induced low density lipoprotein oxidation in a dose-dependent manner. Exposing HepG2 cells to FeSO 4 increased intracellular reactive oxygen species formation and lipid peroxides, which was significantly reduced by treatment with FPM. Furthermore, FPM increased the activities of superoxide dismutase and glutathione peroxidase in cells. FPM recovered the hydrogen peroxide (H 2 O 2 )-induced inhibition of GJIC and attenuated the phosphorylation of connexin 43 (Cx43) and extracellular signal-regulated kinase1/2 (ERK1/2). Taken together, these results demonstrated that FPM has antioxidant activity and protects against H 2 O 2 -induced inhibition of GJIC by blocking phosphorylation of Cx43 via activation of ERK1/2.

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“…Inhibition of gap-junction intercellular communication (GJIC) is strongly related to tumorigenesis and cocoa polyphenol extracts dose dependently attenuated hydrogen peroxide (H 2 O 2 )-induced inhibition of GJIC in rat liver epithelial cells (Fig. 6, Lee et al, 2010) cocoa polyphenol extracts inhibited the H 2 O 2 -induced activation of MEK and ERK and further attenuated the phosphorylation and internalization of connexin 43, a regulating protein of GJIC . Cocoa polyphenol extracts may suppress H 2 O 2 -induced tumorigenesis through GJIC protection.…”

Section: Downloaded By [University Of Utah] At 09:10 27 November 2014mentioning

confidence: 99%

Cocoa Phytochemicals: Recent Advances in Molecular Mechanisms on Health

Kim

Shim

et al. 2014

Critical Reviews in Food Science and Nutrition

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Recent reports on cocoa are appealing in that a food commonly consumed for pure pleasure might also bring tangible benefits for human health. Cocoa consumption is correlated with reduced health risks of cardiovascular diseases, hypertension, atherosclerosis, and cancer, and the health-promoting effects of cocoa are mediated by cocoa-driven phytochemicals. Cocoa is rich in procyanidins, theobromine, (-)-epicatechin, catechins, and caffeine. Among the phytochemicals present in consumed cocoa, theobromine is most available in human plasma, followed by caffeine, (-)-epicatechin, catechin, and procyanidins. It has been reported that cocoa phytochemicals specifically modulate or interact with specific molecular targets linked to the pathogenesis of chronic human diseases, including cardiovascular diseases, cancer, neurodegenerative diseases, obesity, diabetes, and skin aging. This review summarizes comprehensive recent findings on the beneficial actions of cocoa-driven phytochemicals in molecular mechanisms of human health.

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Cocoa polyphenols attenuate hydrogen peroxide-induced inhibition of gap-junction intercellular communication by blocking phosphorylation of connexin 43 via the MEK/ERK signaling pathway☆

Cited by 22 publications

References 33 publications

Gap Junction Intercellular Communication Mediated by Connexin43 in Astrocytes Is Essential for Their Resistance to Oxidative Stress

Gap Junction Intercellular Communication Mediated by Connexin43 in Astrocytes Is Essential for Their Resistance to Oxidative Stress

Antioxidant activity of Fragilariopsis pseudonana and protective effect against hydrogen peroxide-induced inhibition of gap junctional intercellular communication

Cocoa Phytochemicals: Recent Advances in Molecular Mechanisms on Health

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