An Endoplasmic Reticulum Stress-specific Caspase Cascade in Apoptosis

Morishima, Nobuhiro; Nakanishi, Kazuyoshi; Takenouchi, Hiromi; Shibata, Takehiko; Yasuhiko, Yukuto

doi:10.1074/jbc.m204973200

Cited by 810 publications

(291 citation statements)

References 38 publications

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“…By contrast, this staining was not detectable in the presence of SB20358, the specific P38 inhibitor. In search for the mediators of the apoptotic response, we investigated some of the caspases which have been involved in this biological effect (Nakagawa et al ., 2000; Morishima et al ., 2002). Compared with controls, glucose‐deprived cells showed a significant increase in the level of caspase‐3 and caspase‐12, which were blunted in the presence of the P38 inhibitor (Fig.…”

Section: Resultsmentioning

confidence: 99%

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Lauretti

Praticò

2015

Aging Cell

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SummaryAlterations of glucose metabolism have been observed in Alzheimer's disease (AD) brain. Previous studies showed that glucose deprivation increases amyloidogenesis via a BACE‐1‐dependent mechanism. However, no data are available on the effect that this condition may have on tau phosphorylation. In this study, we exposed neuronal cells to a glucose‐free medium and investigated the effect on tau phosphorylation. Compared with controls, cells incubated in the absence of glucose had a significant increase in tau phosphorylation at epitopes Ser202/Thr205 and Ser404, which was associated with a selective activation of the P38 mitogen‐activated protein kinase. Pharmacological inhibition of this kinase prevented the increase in tau phosphorylation, while fluorescence studies revealed its co‐localization with phosphorylated tau. The activation of P38 was secondary to the action of the apoptosis signal‐regulating kinase 1, as its down‐regulation prevented it. Finally, glucose deprivation induced cell apoptosis, which was associated with a significant increase in both caspase 3 and caspase 12 active forms. Taken together, our studies reveal a new mechanism whereby glucose deprivation can modulate AD pathogenesis by influencing tau phosphorylation and suggest that this pathway may be a new therapeutic target for AD.

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Section: Resultsmentioning

confidence: 99%

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Lauretti

Praticò

2015

Aging Cell

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“…In contrast, NB-39-nu cells expressed a large amount of procaspase-8. Procaspase-12, which is involved in the endoplasmic reticulum-stress-induced apoptosis (Nakagawa et al, 2000;Morishima et al, 2002), was readily detectable in all of the neuroblastoma cell lines that we examined, and did not respond to ATRA. Under our experimental conditions, ATRA had negligible effects on proteolytic cleavage of caspase-8 and caspase-12 (data not shown).…”

Section: Atra-induced Apoptotic Cell Death In Neuroblastoma Cellsmentioning

confidence: 95%

Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in neuroblastoma

et al. 2006

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“…ER stress-induced apoptosis has been demonstrated to be regulated in part by caspases (Morishima et al, 2002;Chae et al, 2004). As caspase 2 is differentially expressed in LNCaP and PC3 cells, we tried to determine whether caspase 2, through the ER, is sensing PL treatment.…”

Section: Caspase 2 Is Upregulated In Lncap But Not In Pc3 Cells Aftermentioning

confidence: 99%

“…Persistent protein overload in the ER can trigger apoptosis (Herr and Debatin, 2001;Breckenridge et al, 2003). Damage to the ER activates certain caspase family members, including caspase 2 (Morishima et al, 2002;Chae et al, 2004).…”

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confidence: 99%

Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells

et al. 2007

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It is known that polysaccharides extracted from the Phellinus linteus (PL) mushroom possess antitumour activity. We previously have demonstrated that high doses of PL render murine or human lung cancer cells susceptible to apoptosis. However, the molecular mechanisms of PL-mediated apoptosis have not been fully explored. In this study, we demonstrate that LNCaP cells expressing the androgen receptor (AR) are highly susceptible to apoptosis in response to treatment with high doses of PL. In this process, caspase 8 and its downstream effectors (such as BID), as well as ER stress-related, apoptotic signalling, are activated. In contrast, a moderate amount of apoptosis occurs in PC3 cells (that lack AR) after the same treatment, which does not activate ER-mediated apoptotic signalling. We also show that, in the process of PL-induced apoptosis, caspase 2 is induced in LNCaP cells, but not in PC3 cells. However, LNCaP cells that express a mutated AR or LNCaP cells treated with a caspase 2 inhibitor blocked ER stress-induced apoptotic signals. The magnitudes of the induction of apoptosis in these cells are comparable with what occurred in the PC3 cells. The data demonstrate that high doses of PL activate the AR-dependent and independent apoptotic pathways. Our study also suggests that caspase 2 is a key target in the determination of the susceptibility of prostate cancer cells to PL-induced apoptosis. Phellinus linteus (PL) is among a number of well-known medicinal mushrooms from Asian countries, which have been taken orally since ancient times as a health-promoting dietary supplement and an adjuvant to combat viral and bacterial infections. PL, after purification, shows a relatively homogeneous molecular weight distribution on gel permeation HPLC and is estimated to be around 150 kDa from the retention time on HPLC pullulan molecular markers (Song et al, 1995). The main components of PL are polysaccharides (Song et al, 1995;Lorenzen and Anke, 1998;Borchers et al, 1999;Han et al, 1999). Many studies demonstrated that polysaccharides from various substances, including PL, are remarkably effective in inhibiting the growth of tumours without toxic side effects. Studies also showed that polysaccharides in PL are able to suppress tumours, either indirectly by enhancing the host's immune system or directly by inducing apoptosis in tumour cells (Chihara et al, 1969;Chung et al, 1982;Cun et al, 1994;Wasser, 2002;Collins et al, 2006;Guo et al, 2006). Therefore, the antitumour, antiangiogenic and immunomodulatory effects of PL are potential areas for developing novel pharmaceutical products. However, the underlying molecular mechanisms of the antitumour effects of PL have not yet been fully explored.Changes in the androgen receptor (AR) have been indicated to contribute to the development of prostate cancer and are a serious challenge to effective treatment. Mutations in the AR can increase its affinity for ligand binding, permitting activation by nonandrogenic hormones or even antagonists (Nelson et al, 2003;Debes and Tindall, ...

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An Endoplasmic Reticulum Stress-specific Caspase Cascade in Apoptosis

Abstract: insensitive to ER stress, thereby suppressing apoptosis and the activation of caspase-9 and -3. These data suggest that procaspase-9 is a substrate of caspase-12 and that ER stress triggers a specific cascade involving caspase-12, -9, and -3 in a cytochrome c-independent manner.

Cited by 810 publications

References 38 publications

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in neuroblastoma

Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells

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