Role of mitogen-activated protein kinases in hydrogen peroxide-induced cell death in osteoblastic cells

Park, Byung Guk; Yoo, Chong Il; Kim, Hui Taek; Kwon, Chae Hwa; Kim, Yong Keun

doi:10.1016/j.tox.2005.07.003

Cited by 109 publications

(75 citation statements)

References 56 publications

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“…Although ERK activation is primarily associated with cell survival (Cobb et al, 1991;Kultz and Burg, 1998), we found reduced activity of this kinase in cells overexpressing RAC3. Such findings are in agreement with results of other studies suggesting that under some circumstances, ERK exists as a pro-apoptotic pathway (Park et al, 2005). These observations should be viewed in the context of the occasionally conflicting roles that MAPKs are believed to play in survival signaling (Downward, 1998;Kultz and Burg, 1998;Ono and Han, 2000;Franco et al, 2002;Park et al, 2005).…”

Section: Discussionsupporting

confidence: 91%

The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action

et al. 2007

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The p160 nuclear receptor co-activators represent a family of molecules, which are recruited by steroid nuclear receptors as well as other transcription factors that are overexpressed in several tumors. We investigated the role of one member of this family on the sensitivity of cells to apoptosis. We observed that overexpression of the RAC3 (receptor-associated co-activator-3) p160 co-activator inhibits hydrogen peroxide-induced cell death in human embryonic kidney 293 (HEK293) cells. The mechanism involves the activation of anti-apoptotic pathways mediated through enhanced nuclear factor kappa B (NFjB) activity, inhibition of caspase-9 activation, diminished apoptotic-inducing factor (AIF) nuclear localization and a change in the activation pattern of several kinases, including an increase in both AKT and p38 kinase activities, and inhibition of ERK2. Moreover, RAC3 has been found associated with a protein complex containing AIF, Hsp90 and dynein, suggesting a role for the coactivator in the cytoplasmatic nuclear transport of these proteins associated with cytoskeleton. These results demonstrate that there are several molecular pathways that could be affected by their overexpression, including those not restricted to steroid regulation or the nuclear action of co-activators, which results in diminished sensitivity to apoptosis. Furthermore, this could represent one mechanism by which co-activators contribute to tumor development.

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Section: Discussionsupporting

confidence: 91%

The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action

et al. 2007

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“…During apoptosis induced by a variety of stimuli, Bax is translocated to the mitochondria, where it promotes the release of proapoptotic proteins from the intermembrane space (Degli Esposti and Dive, 2003). In renal epithelial and osteoblastic cells, Bax expression is increased after cisplatin or H 2 O 2 , and inhibition of the ERK pathway decreased Bax expression Park et al, 2005). Similar to the role of ERK in the regulation of Bax expression, ERK activation is also associated with up-regulation of p53 expression in HeLa cells treated with shikonin (a red naphthoquinone pigment isolated from the ground rhizome of lithospermum erythrorhizon) (Wu et al, 2005) and in lens epithelial cells treated with calcimycin, a calcium mobilizer (Li et al, 2005).…”

Section: Mechanisms Of Erk-induced Apoptosis Erk-mediated Regulation mentioning

confidence: 99%

A Death-Promoting Role for Extracellular Signal-Regulated Kinase

Zhuang

Schnellmann

2006

J Pharmacol Exp Ther

330

273

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Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), which are members of the mitogen-activated protein kinase superfamily, have been well characterized and are known to be involved in cell survival; however, recent evidence suggests that the activation of ERK1/2 also contributes to cell death in some cell types and organs under certain conditions. For example, ERK1/2 is activated in neuronal and renal epithelial cells upon exposure to oxidative stress and toxicants and deprivation of growth factors, and inhibition of the ERK pathway blocks apoptosis. ERK activation also occurs in animal models of ischemia-and trauma-induced brain injury and cisplatin-induced renal injury, and inactivation of ERK reduces the extent of tissue damage. In some studies, ERK has been implicated in apoptotic events upstream of mitochondrial cytochrome c release, whereas other studies have suggested the converse that ERK acts downstream of mitochondrial events and upstream of caspase-3 activation. ERK also can contribute to cell death through the suppression of the antiapoptotic signaling molecule Akt. Here we summarize the evidence and mechanism of ERK-induced apoptosis in both cell culture and in animal models.

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“…Several studies have shown that oxidative stress elicited by various stimuli is associated with activation of the extracellular signal-regulated kinase (ERK1/2) mitogen activated protein kinase (MAPK) pathway (12,13), which could participate in pathways influencing protein breakdown (5,14,15). In turn, ERK1/2 activation can be inhibited by antioxidants (10).…”

Section: Uchenne Muscular Dystrophy (Dmd) Is a Progressivementioning

confidence: 99%

L-Glutamine Administration Reduces Oxidized Glutathione and MAP Kinase Signaling in Dystrophic Muscle of mdx Mice

et al. 2008

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ABSTRACT:To determine whether glutamine (Gln) reduces the ratio of oxidized to total glutathione (GSSG/GSH) and extracellular signal-regulated kinase (ERK1/2) activation in dystrophic muscle. Four-week old mdx mice, an animal model for Duchenne muscular dystrophy and control (C57BL/10) received daily intraperitoneal injections of L-Gln (500 mg/kg/d) or 0.9% NaCl for 3 d. GSH and GSSG concentrations in gastrocnemius were measured using a standard enzymatic recycling procedure. Free amino acid concentrations in gastrocnemius were determined by ion exchange chromatography. Phosphorylated protein levels of ERK1/2 in quadriceps were examined using Western Blot. L-Gln decreased GSSG and GSSG/GSH (an indicator of oxidative stress). This was associated with decreased ERK1/2 phosphorylation. Muscle free Gln, glutamate (Glu), and the sum (Gln ϩ Glu) were higher in mdx versus C57BL/10, at the basal level. Exogenous Gln decreased muscle free Glu and Gln ϩ Glu in mdx only, whereas Gln was not affected. In conclusion, exogenous Gln reduces GSSG/GSH and ERK1/2 activation in dystrophic skeletal muscle of young mdx mice, which is associated with decreased muscle free Glu and Gln ϩ Glu. This antioxidant protective mechanism provides a molecular basis for Gln's antiproteolytic effect in Duchenne muscular dystrophy children.

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Role of mitogen-activated protein kinases in hydrogen peroxide-induced cell death in osteoblastic cells

Cited by 109 publications

References 56 publications

The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action

The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action

A Death-Promoting Role for Extracellular Signal-Regulated Kinase

L-Glutamine Administration Reduces Oxidized Glutathione and MAP Kinase Signaling in Dystrophic Muscle of mdx Mice

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