Regulation of Bcl-2 phosphorylation in response to oxidative stress in cardiac myocytes

Markou, Thomais; Dowling, Aileen; Kelly, Tara; Lazou, Antigone

doi:10.1080/10715760903071649

Cited by 42 publications

(30 citation statements)

References 37 publications

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“…Also, the current study revealed marginal induction of JNK1/2 during Bcl-2 upregulation that supported the inverse relationship of Bcl-2 and JNK1/2 expression. This has been reinforced by other reports which show that the stimulation of cardiac myocytes with 0.2 mM H 2 O 2 induces apoptosis with a marked downregulation of Bcl-2 protein (Markou et al 2009). Dunschede et al (2008) have reported that Bcl-2 upregulation may protect against the postischemic burst of ROS and therefore suppresses apoptotic-related cell death.…”

Section: Bcl-2 Upregulation Is Required For the Inhibition Of Hepatocsupporting

confidence: 56%

Heat-shock protein 90 alpha (HSP90α) modulates signaling pathways towards tolerance of oxidative stress and enhanced survival of hepatocytes of Mugil cephalus

Perumal

Rani

2011

Cell Stress and Chaperones

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Oxidative stress causes damage at the cellular level and activates a number of signaling pathways. Earlier, we have demonstrated that pollutant-related oxidative stress upregulates heat-shock protein 90 alpha (HSP90α) against stress insult in hepatocytes of Mugil cephalus living in a polluted estuary. However, the impact of pollution-induced HSP90α upregulation on stress tolerance is not clear. Here we propose that the effect of stress resistance depends on the ability of HSP90α to modulate the signaling pathways involving proteins such as apoptosis signal-regulating kinase 1, c-Jun NH 2 -terminal protein kinase 1/2, signal transducers and activators of transcription, extracellular signal-regulated kinase 1/2, protein kinase B, nuclear factor-kappa binding, Ets-like protein 1, and B cell lymphoma-2. In order to investigate this, the activation of HSP90α-associated signaling molecules was examined by Western blotting and immunohistochemistry. The relationship between the protein expression patterns was identified by Spearman's rank correlation analysis. The signaling proteins exhibited differential modulation as revealed from their expression patterns in pollutant-exposed fish hepatocytes, in comparison with the control fish hepatocytes. The results suggested that in spite of the prevalence of oxidative stress in pollutantexposed fish hepatocytes, the stress-mediated induction of HSP90α enabled the hepatocytes to become stress tolerant and to survive by modulating the actions of key proteins and kinases in the signal transduction pathways.

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Section: Bcl-2 Upregulation Is Required For the Inhibition Of Hepatocsupporting

confidence: 56%

Heat-shock protein 90 alpha (HSP90α) modulates signaling pathways towards tolerance of oxidative stress and enhanced survival of hepatocytes of Mugil cephalus

Perumal

Rani

2011

Cell Stress and Chaperones

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“…Considering that apoptosis was induced in cancer cells in a short time after OA treatment, we focused our study on if p38 MAPK phosphorylated and activated pro-apoptotic proteins in OA-stimulated cancer cells. To date, phosphorylations of Bax, Bim and Bcl-2 by p38 MAPK have been reported to facilitate the induction of apoptosis (Rosini et al, 2000;Cai et al, 2006;Capano et al, 2006;Kim et al, 2006;Markou et al, 2009). The early phosphorylation (3-6 hr after stilumation) of apoptosisrelated proteins Bax, Bim and Bcl-2 was detected in cancer cells treated with OA, as well as the subsequent translation of Bax and Bim ( Figure 4A and 4B).…”

Section: Discussionmentioning

confidence: 89%

p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid

Liu¹,

Wu²,

Ma³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Oleanolic acid (OA) is a nutritional component widely distributed in various vegetables. Although it has been well recognized for decades that OA exerts certain anti-tumor activity by inducing mitochondria-dependent apoptosis, it is still unclear that what molecular signaling is responsible for this effect. In this study, we employed cancer cell lines, A549, BXPC-3, PANC-1 and U2OS to elucidate the molecular mechanisms underlying OA antitumor activity. We found that activation of MAPK pathways, including p-38 MAPK, JNK and ERK, was triggered by OA in both a dose and time-dependent fashion in all the tested cancer cells. Activation was accompanied by cleavage of caspases and PARP as well as cytochrome C release. SB203580 (p38 MAPK inhibitor), but not SP600125 (JNK inhibitor) and U0126 (ERK inhibitor), rescued the pro-apoptotic effect of OA on A549 and BXPC-3 cells. OA induced p38 MAPK activation promoted mitochondrial translocation of Bax and Bim, and inhibited Bcl-2 function by enhancing their phosphorylation. OA can induce reactive oxygen species (ROS)-dependent ASK1 activation, and this event was indispensable for p38 MAPK-dependent apoptosis in cancer cells. In vivo, p38 MAPK knockdown A549 tumors proved resistant to the growth-inhibitory effect of OA. Collectively, we elucidated that activation of ROS/ASK1/p38 MAPK pathways is responsible for the apoptosis stimulated by OA in cancer cells. Our finding can contribute to a better understanding of molecular mechanisms underlying the antitumor activity of nutritional components.

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“…Moreover, pretreatment with MG132 suppresses BCL2 down-regulation in quinacrine-treated cells. Previous studies revealed that activation of p38 MAPK by oxidative stress results in the phosphorylation and degradation of BCL2 (Markou et al, 2009). Moreover, dephosphorylation of BCL2 by protein phosphatase 2A protects BCL2 from proteasomedependent degradation .…”

Section: Resultsmentioning

confidence: 99%

Quinacrine induces apoptosis in human leukemia K562 cells via p38 MAPK-elicited BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression

Changchien

Chen

Huang

et al. 2015

Toxicology and Applied Pharmacology

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Regulation of Bcl-2 phosphorylation in response to oxidative stress in cardiac myocytes

Cited by 42 publications

References 37 publications

Heat-shock protein 90 alpha (HSP90α) modulates signaling pathways towards tolerance of oxidative stress and enhanced survival of hepatocytes of Mugil cephalus

Heat-shock protein 90 alpha (HSP90α) modulates signaling pathways towards tolerance of oxidative stress and enhanced survival of hepatocytes of Mugil cephalus

p38 MAPK Signaling Mediates Mitochondrial Apoptosis in Cancer Cells Induced by Oleanolic Acid

Quinacrine induces apoptosis in human leukemia K562 cells via p38 MAPK-elicited BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression

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