Role for PKC-ε in neuronal death induced by oxidative stress

Jung, Yi Sook; Ryu, Bo Rum; Lee, Bo Kyung; Mook‐Jung, Inhee; Kim, Seung Up; Lee, Soo Hwan; Baik, Eun Joo; Moon, Chang Hyun

doi:10.1016/j.bbrc.2004.05.217

Cited by 36 publications

(25 citation statements)

References 30 publications

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“…PKCe has been implicated in the regulation of cell apoptosis in various cellular systems (9)(10)(11)(12). To examine the role of PKCe in glioma cell apoptosis, we first employed the apoptotic stimulus TRAIL and the A172 glioma cells which are highly sensitive to this ligand.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, overexpression of PKCq protected MCF-7 cells from tumor necrosis factor (TNF)-ainduced apoptosis (9) and promoted the survival of lung cancer cells (10). In contrast, PKCq has been shown to mediate neuronal death induced by oxidative stress (11) and the apoptosis of macrophages in response to lipopolysaccharide via c-Jun NH 2 -terminal kinase (JNK) activation (12). PKCq is overexpressed in gliomas (13,14); however, its role in the regulation of glioma cell apoptosis has not been extensively studied.…”

Section: Introductionmentioning

confidence: 99%

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Protein Kinase C-ε Regulates the Apoptosis and Survival of Glioma Cells

et al. 2005

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In this study, we examined the role of protein kinase C (PKC)-E in the apoptosis and survival of glioma cells using tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-stimulated cells and silencing of PKCE expression. Treatment of glioma cells with TRAIL induced activation, caspasedependent cleavage, and down-regulation of PKCE within 3 to 5 hours of treatment. Overexpression of PKCE inhibited the apoptosis induced by TRAIL, acting downstream of caspase 8 and upstream of Bid cleavage and cytochrome c release from the mitochondria. A caspase-resistant PKCE mutant (D383A) was more protective than PKCE, suggesting that both the cleavage of PKCE and its down-regulation contributed to the apoptotic effect of TRAIL. To further study the role of PKCE in glioma cell apoptosis, we employed short interfering RNAs directed against the mRNA of PKCE and found that silencing of PKCE expression induced apoptosis of various glioma cell lines and primary glioma cultures. To delineate the molecular mechanisms involved in the apoptosis induced by silencing of PKCE, we examined the expression and phosphorylation of various apoptosis-related proteins. We found that knockdown of PKCE did not affect the expression of Bcl2 and Bax or the phosphorylation and expression of Erk1/2, c-Jun-NH 2 -kinase, p38, or STAT, whereas it selectively reduced the expression of AKT. Similarly, TRAIL reduced the expression of AKT in glioma cells and this decrease was abolished in cells overexpressing PKCE. Our results suggest that the cleavage of PKCE and its down-regulation play important roles in the apoptotic effect of TRAIL. Moreover, PKCE regulates AKT expression and is essential for the survival of glioma cells. (Cancer Res 2005; 65(16): 7301-9)

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protein Kinase C-ε Regulates the Apoptosis and Survival of Glioma Cells

et al. 2005

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“…In l-buthionine-S,R-sulfoximine (BSO) treated neurons, a burst of ROS leads to neuronal cell death. In this case, inhibition of PKCε correlated with neuron survival rather than cell death [78]. In a rodent stroke model, moderate hypothermia was reported to preserve PKCε activity [79].…”

Section: Pkcγ and Pkcε In Neural Tissuesmentioning

confidence: 88%

Protein kinase C as a stress sensor

Barnett

Madgwick

Takemoto

2007

Cellular Signalling

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While there are many reviews which examine the group of proteins known as protein kinase C (PKC), the focus of this article is to examine the cellular roles of two PKCs that are important for stress responses in neurological tissues (PKCγ and ε) and in cardiac tissues (PKCε). These two kinases, in particular, seem to have overlapping functions and interact with an identical target, connexin 43 (Cx43), a gap junction protein which is central to proper control of signals in both tissues. While PKCγ and PKCε both help protect neural tissue from ischemia, PKCε is the primary PKC isoform responsible for responding to decreased oxygen, or ischemia, in the heart. Both do this through Cx43.It is clear that both PKCγ and PKCε are necessary for protection from ischemia. However, the importance of these kinases has been inferred from preconditioning experiments which demonstrate that brief periods of hypoxia protect neurological and cardiac tissues from future insults, and that this depends on the activation, translocation, or ability for PKCγ and/or PKCε to interact with distinct cellular targets, especially Cx43.This review summarizes the recent findings which define the roles of PKCγ and PKCε in cardiac and neurological functions and their relationships to ischemia/reperfusion injury. In addition, a biochemical comparison of PKC γ and PKC ε and a proposed argument for why both forms are present in neurological tissue while only PKC ε is present in heart, are discussed. Finally, the biochemistry of PKCs and future directions for the field are discussed, in light of this new information.

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“…Since PKC has been implicated as having a regulatory role in both TNF␣-initiated signaling events and TMT toxicity (Pavlakovic et al, 1995;Basu et al, 2002), the functional role of PKC in Snn gene expression is not surprising. Studies have demonstrated that PKC⑀ is involved in several cellular processes, including cellular proliferation (Akita, 2002;Soh and Weinstein, 2003), cell death (Comalada et al, 2003;Jung et al, 2004), and the immune response (Aksoy et al, 2004). The apparent regulation of stannin by PKC⑀ is supported by the observation that stimulation of PKC⑀ in vitro results in cell death in response to lipopolysaccharide (Comalada et al, 2003) and oxidative stress (Jung et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase Cϵ Regulates Tumor Necrosis Factor-α-Induced Stannin Gene Expression

Reese

Davidson

Billingsley³

et al. 2005

J Pharmacol Exp Ther

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Stannin (Snn) is a highly conserved vertebrate protein that has been closely linked to trimethyltin (TMT) toxicity. We have previously demonstrated that Snn is required for TMT-induced cell death. Others have shown that TMT exposure results in tumor necrosis factor-␣ (TNF␣) production and that TNF␣ treatment induces Snn gene expression in human umbilical vein endothelial cells (HUVECs). In this study, we investigated a signaling mechanism by which Snn gene expression is regulated by TMT and demonstrated that TNF␣ stimulates Snn gene expression in a protein kinase C⑀-dependent manner in HUVECs in response to TMT exposure. Supporting this, we show that TMTinduced toxicity is significantly blocked by pretreatment with an anti-TNF␣ antibody in HUVECs. Using a quantitative real-time polymerase chain reaction assay, we also show that the level of Snn gene expression is significantly increased in HUVECs in response to either TMT or TNF␣ treatment. This TNF␣-induced Snn gene expression is blocked when HUVECs were pretreated with bisindolylmaleimide I, an inhibitor of protein kinase C (PKC). In contrast, when HUVECs were treated with phorbol 12-myristate 13-acetate, a PKC activator, we observed a significant increase in Snn gene expression. Using isotypespecific siRNA against PKC, we further show that knockdown of PKC⑀, but not PKC␦ or PKC, significantly blocked TNF␣-induced Snn gene expression. Together, these results indicate that TNF␣-induced, PKC⑀-dependent Snn expression may be a critical factor in TMT-induced cytotoxicity.

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Role for PKC-ε in neuronal death induced by oxidative stress

Cited by 36 publications

References 30 publications

Protein Kinase C-ε Regulates the Apoptosis and Survival of Glioma Cells

Protein Kinase C-ε Regulates the Apoptosis and Survival of Glioma Cells

Protein kinase C as a stress sensor

Protein Kinase Cϵ Regulates Tumor Necrosis Factor-α-Induced Stannin Gene Expression

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