Okadaic acid induces JNK activation, bim overexpression and mitochondrial dysfunction in cultured rat cortical neurons

Yoon, Sun-Young; Choi, Jin-Won; Yoon, Juhee; Huh, Jae-Wan; Kim, Dong-Hou

doi:10.1016/j.neulet.2005.10.034

Cited by 32 publications

(19 citation statements)

References 35 publications

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“…This treatment nearly abolished ERK1/2 signaling. Multiple studies using a variety of cytokine and toxic stimuli document that JNK1-3 activation in astrocytes, neurons, and transformed versions of these cells can trigger cell death (37). The balance between the readouts of ERK1/2 and JNK1-3 signaling may represent a key homeostatic mechanism that regulates cell survival versus cell death processes (38).…”

Section: Discussionmentioning

confidence: 99%

Caspase-, cathepsin-, and PERK-dependent regulation of MDA-7/IL-24-induced cell killing in primary human glioma cells

Yacoub

Park

Gupta

et al. 2008

Molecular Cancer Therapeutics

104

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Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a novel cytokine displaying selective apoptosis-inducing activity in transformed cells without harming normal cells. The present studies focused on defining the mechanism(s) by which a GST-MDA-7 fusion protein inhibits cell survival of primary human glioma cells in vitro. GST-MDA-7 killed glioma cells with diverse genetic characteristics that correlated with inactivation of ERK1/2 and activation of JNK1-3. Activation of JNK1-3 was dependent on protein kinase R -like endoplasmic reticulum kinase (PERK), and GST-MDA-7 lethality was suppressed in PERKÀ/À cells. JNK1-3 signaling activated BAX, whereas inhibition of JNK1-3, deletion of BAX, or expression of dominant-negative caspase-9 suppressed lethality. GST-MDA-7 also promoted a PERK-, JNK-, and cathepsin B -dependent cleavage of BID; loss of BID function promoted survival. GST-MDA-7 suppressed BAD and BIM phosphorylation and heat shock protein 70 (HSP70) expression. GST-MDA-7 caused PERK-dependent vacuolization of LC3-expressing endosomes whose formation was suppressed by incubation with 3-methyladenine, expression of HSP70 or BiP/GRP78, or knockdown of ATG5 or Beclin-1 expression but not by inhibition of the JNK1-3 pathway. Knockdown of ATG5 or Beclin-1 expression or overexpression of HSP70 reduced GST-MDA-7 lethality. Our data show that GST-MDA-7 induces an endoplasmic reticulum stress response that is causal in the activation of multiple proapoptotic pathways, which converge on the mitochondrion and highlight the complexity of signaling pathways altered by mda-7/IL-24 in glioma cells that ultimately culminate in decreased tumor cell survival. [Mol Cancer Ther 2008;7(2):297 -313]

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Section: Discussionmentioning

confidence: 99%

Caspase-, cathepsin-, and PERK-dependent regulation of MDA-7/IL-24-induced cell killing in primary human glioma cells

Yacoub

Park

Gupta

et al. 2008

Molecular Cancer Therapeutics

104

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“…Multiple studies using a variety of cytokine and toxic stimuli have shown that JNK1-3 activation in astrocytes, neurons, and transformed versions of these cells can cause cell death (37,38). The balance between the outputs of ERK1/2 and AKT signaling and that of JNK1-3 signaling has been argued to represent a key homeostatic mechanism, which regulates cell survival versus cell death processes (39,40).…”

Section: Discussionmentioning

confidence: 99%

Regulation of GST-MDA-7 toxicity in human glioblastoma cells by ERBB1, ERK1/2, PI3K, and JNK1-3 pathway signaling

Yacoub

Gupta

Park

et al. 2008

Molecular Cancer Therapeutics

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“…Other suggested mechanisms have included oxidative stress–induced enhancement of APP processing and decreased A β degradation due to either a decrease in lysosomal enzyme activity or a structural modification of A β that would make it more resistant to hydrolysis. Oxidative stress and damage in AD have also been proposed to lead to autophagy of mitochondria with an accumulation of mitochondrial degradation products also in the lysosomal pathway 60– 62…”

Section: Aberrant Induction and A Dysfunctional Autophagic Pathwaymentioning

confidence: 99%

Cell “Self‐Eating” (Autophagy) Mechanism in Alzheimer's Disease

Funderburk

Marcellino

Yue

2010

Mount Sinai J Medicine

119

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The autophagy pathway is the major degradation pathway of the cell for long-lived proteins and organelles. Dysfunction of autophagy has been linked to several neurodegenerative disorders that are associated with an accumulation of misfolded protein aggregates. Alzheimer's disease, the most common neurodegenerative disorder, is characterized by 2 aggregate forms, tau tangles and amyloid-β plaques. Autophagy has been linked to Alzheimer's disease pathogenesis through its merger with the endosomallysosomal system, which has been shown to play a role in the formation of the latter amyloid-β plaques. However, the precise role of autophagy in Alzheimer's disease pathogenesis is still under contention. One hypothesis is that aberrant autophagy induction results in an accumulation of autophagic vacuoles containing amyloid-β and the components necessary for its generation, whereas other evidence points to impaired autophagic clearance or even an overall reduction in autophagic activity playing a role in Alzheimer's disease pathogenesis. In this review, we discuss the current evidence linking autophagy to Alzheimer's disease as well as the uncertainty over the exact role and level of autophagic regulation in the pathogenic mechanism of Alzheimer's disease. Mt Sinai J Med 77:59-68, 2010.  2010 Mount Sinai School of Medicine

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Okadaic acid induces JNK activation, bim overexpression and mitochondrial dysfunction in cultured rat cortical neurons

Cited by 32 publications

References 35 publications

Caspase-, cathepsin-, and PERK-dependent regulation of MDA-7/IL-24-induced cell killing in primary human glioma cells

Caspase-, cathepsin-, and PERK-dependent regulation of MDA-7/IL-24-induced cell killing in primary human glioma cells

Regulation of GST-MDA-7 toxicity in human glioblastoma cells by ERBB1, ERK1/2, PI3K, and JNK1-3 pathway signaling

Cell “Self‐Eating” (Autophagy) Mechanism in Alzheimer's Disease

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