ERK and JNK mediate TNFα-induced p53 activation in apoptotic and autophagic L929 cell death

Cheng, Yan; Qiu, Feng; Tashiro, Shin‐ichi; Onodera, Satoshi; Ikejima, Takashi

doi:10.1016/j.bbrc.2008.09.018

Cited by 122 publications

(93 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In any case, autophagy may activate endoplasmic reticulum stress or oxidative stress during digestion of endoplasmic reticulum or mitochondria, which may activate JNK signaling pathway. In contrast to our findings, several investigators have described that JNK activation occurred upstream of the induction of autophagy or autophagic cell death when various cells are starved (Wei et al, 2008), treated with tumor necrosis factor (Cheng et al, 2008) and ceramide (Li et al, 2009). Possible explanation for this discrepancy might be the difference of the cell types or stimuli used.…”

Section: Discussioncontrasting

confidence: 99%

Involvement of JNK in the regulation of autophagic cell death

et al. 2010

View full text Add to dashboard Cite

Programmed cell death is a crucial process in the normal development and physiology of metazoans, and it can be divided into several categories that include type I death (apoptosis) and type II death (autophagic cell death). The Bcl-2 family proteins are well-characterized regulators of apoptosis, among which multidomain pro-apoptotic members (such as Bax and Bak) function as a mitochondrial gateway at which various apoptotic signals converge. Although embryonic fibroblasts from Bax/Bak doubleknockout (DKO) mice are resistant to apoptosis, we have previously reported that these cells still die by autophagy in response to various death stimuli. In this study, we found that jun N-terminal kinase (JNK) was activated in etoposide-and staurosporine-treated, but not serumstarved, Bax/Bak DKO cells, and that autophagic cell death was suppressed by the addition of a JNK inhibitor and by a dominant-negative mutant of JNK. Studies with sek1À/À cells revealed that disruption of JNK prevented the induction of autophagic cell death. Coactivation of JNK and autophagy induced autophagic cell death. Activation of JNK occurred downstream of the induction of autophagy, and was dependent on the autophagic process. These results indicate that JNK activation is crucial for the autophagic death of Bax/ Bak DKO cells.

show abstract

Section: Discussioncontrasting

confidence: 99%

Involvement of JNK in the regulation of autophagic cell death

et al. 2010

View full text Add to dashboard Cite

show abstract

“…In the present study, it was revealed that Akt/mTOR had a negatively regulatory role in PM 2.5 -induced autophagy in Beas-2B cells. However, this autophagy was independent of JNK, concurrent with previous findings (33)(34)(35), indicating that a different MAPK response to PM 2.5 is dependent on cell-type specification.…”

Section: Discussionsupporting

confidence: 88%

Particulate matter 2.5 induces autophagy via inhibition of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin kinase signaling pathway in human bronchial epithelial cells

Wang

et al. 2015

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Particulate matter 2.5 (PM 2.5 ) is a significant risk factor for asthma. A recent study revealed that autophagy was associated with asthma pathogenesis. However, the specific mechanisms underlying PM 2.5 -induced autophagy in asthma have remained elusive. In the present study, PM 2.5 -induced autophagy was evaluated in Beas-2B human bronchial epithelial cells and the potential molecular mechanisms were investigated. Using electron microscopy, immunofluorescence staining and immunoblot studies, it was confirmed that PM 2.5 induced autophagy in Beas-2B cells as a result of PM 2.5 -mediated inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in Beas-2B cells. LY294002, a PI3K inhibitor, reduced the accumulation of microtubule-associated protein 1 light chain 3 II and attenuated the effect of PM 2.5 . Phosphorylated (p-)p38, p-extracellular signal-regulated kinase and p-c-Jun N-terminal kinase were dephosphorylated following exposure to PM 2.5 . The roles of p53, reactive oxygen species scavenger tetramethylthiourea and autophagy inhibitor 3-methyladenine in PM 2.5 -induced autophagy in Beas-2B cells were also investigated. The results suggested that the PI3K/Akt/mTOR signaling pathway may be a key contributor to PM 2.5 -induced autophagy in Beas-2B cells. The results of the present study therefore provided an a insight into potential future clinical applications targeting these signaling pathways, for the prevention and/or treatment of PM 2.5 -induced lung diseases. IntroductionAcute and chronic exposure to particulate matter (PM), particularly fine particles with aerodynamic diameters of ≤2.5 µm PM 2.5 , has been shown to increase the number of hospital admissions for respiratory causes amongst the general population (1). Evidence obtained from environmental and epidemiological studies has revealed a marked association between fine particulate air pollution and multiple health issues, including respiratory illnesses (for example, respiratory track inflammation, asthma, acute bronchitis and lung cancer) as well as cardiovascular disease mortality (2-4).Increasing evidence supporting a link between traffic-associated air pollution and the incidence of childhood asthma has emerged; however, published estimates highlight the variability observed between populations (5,6). Asthma is a common worldwide respiratory symptom complex, frequently involving airway inflammation, which results in clinically significant physiological airway dysfunction. Asthma pathogenesis is complex, and multiple factors have roles in the development of the disease (7).Autophagy describes an evolutionarily conserved and tightly regulated lysosomal pathway, responsible for the degradation of macromolecules, including proteins, glycogen, lipids, nucleotides and organelles, via several complex pathways (8).Particulate matter 2.5 induces autophagy via inhibition of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin kinase signaling pathway in human bronchial epithelial ...

show abstract

“…The presence of the JNK inhibitor completely abrogated the p53 phosphorylation, indicating that the p53 activation was induced by JNK activation. A recent study also showed that TNFa-mediated JNK activation induced p53 phosphorylation to promote autophagy [12]. To further determine the role of p53 activation in HW1-induced autophagic cell death, we examined celldeath inducing activity of HW1 for the isogenic wild type and p53 À/À HCT116 cells.…”

Section: Hw1-induced Jnk Activation Mediated Upregulation Of Beclin-1mentioning

confidence: 99%

“…In the cytoprotective autophagy induced by external stimuli, the activation of c-Jun NH2-terminal kinase (JNK), also referred to as stress-activated kinases, upregulated Beclin-1 expression [10] and mediated Bcl-2 phosphorylation [9], thereby promoting cellular survival. In other cellular settings, JNK activation has also been essential for autophagic cell death induced by tumor necrosis factor-a (TNFa) [11,12], anti-cancer agents [10], and chemicals [6,8]. We also recently reported that an agonistic antibody (Ab), single chain variable fragment (scFv) HW1, which specifically bound to TNF-related apoptosis inducing ligand (TRAIL) receptor 2 (death receptor 5 (DR5)), triggered autophagic cell death of cancer cells dominantly through JNK pathway in a caspase-independent manner [13].…”

Section: Introductionmentioning

confidence: 99%