NGF-induced phosphatidylinositol 3-kinase signaling pathway prevents thapsigargin-triggered ER stress-mediated apoptosis in PC12 cells

Shimoke, Koji; Kishi, Soichiro; Utsumi, Takahiro; Shimamura, Yuichi; Sasaya, Harue; Oikawa, Tadao; Uesato, Shinichi; Ikeuchi, Toshihiko

doi:10.1016/j.neulet.2005.07.030

Cited by 30 publications

(28 citation statements)

References 17 publications

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“…homeostasis is more likely to have an adverse effect on proliferating cells [37]. The apoptosis-inducing effect of thapsigargin on PC12 cells has been clearly established [38,39]. Since the target for TG is the endoplasmic reticulum Ca 2?…”

Section: Discussionmentioning

confidence: 99%

“…This is likely due to alternative pathway by caspase-3/7 processing at the adjacent D 94 site (Fig. 10) [38]. Until now, the only caspase-12 cleavage-specific consensus sequence corresponds to that of the autoproteolytic cleavage D 318 site that contains the tetrapeptide ATAD and is the basis for commercially available caspase-12 enzyme assays.…”

Section: Discussionmentioning

confidence: 99%

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Calpain and caspase processing of caspase-12 contribute to the ER stress-induced cell death pathway in differentiated PC12 cells

et al. 2010

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Neuronal cell death after traumatic brain injury, Alzheimer's disease and ischemic stroke may in part be mediated through endoplasmic reticulum (ER) stress and unfolded protein response (UPR). UPR results in induction of molecular chaperone GRP78 and the ER-resident caspase-12, whose activation has been proposed to be mediated by calpain and caspase processing, although their relative contribution remains unclear. In this study we induced ER stress with thapsigargin (TG), and determined the activation profile of calpain-2, caspase-3, caspase-7, and caspase-12 by analyses of protein levels, corresponding substrates and breakdown products (BDP). Specific calpain and caspase activity was assessed by analysis of αII-spectrin BDP of 145 kDa (SBDP145), BDP of 150 kDa (SBDP150) and BDP of 120 kDa (SBDP120). Decrease in pro-calpain-2 protein and increased SBDP145 levels by 3 h after TG treatment indicated early calpain activity. Active caspase-7 (p20) increase occurred after 8 h, followed by concomitant up-regulation of active caspase-3 and SBDP120 after 24 h. In vitro digestion experiments supported that SBDP120 was exclusively generated by active caspase-3 and validated that kinectin and co-chaperone p23 were calpain and caspase-7 substrates, respectively. Pro-caspase-12 protein processing by the specific action of calpain and caspase-3/7 was observed in a time-dependent manner. N-terminal pro-domain processing of pro-caspase-12 by calpain generated a 38 kDa fragment, while caspase-3/7 generated a 35 kDa fragment. Antibody developed specifically against the caspase-3/7 C-terminal cleavage site D(341) detected the presence of large subunit (p20) containing 23 kDa fragment that increased after 24 h of TG treatment. Significant caspase-12 enzyme activity was only detected after 24 h of TG treatment and was completely inhibited by caspase 3/7 inhibitor DEVD-fmk and partially by calpain inhibitor SNJ-1945. ER-stress-induced cell death pathway in TG-treated PC12 cells was characterized by up-regulation of GRP-78 and processing and activation of caspase-12 by the orchestrated proteolytic activity of calpain-2 and caspase-3/7.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Calpain and caspase processing of caspase-12 contribute to the ER stress-induced cell death pathway in differentiated PC12 cells

et al. 2010

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“…In addition, an ordinary apoptosis mechanism was also present [4,5]. We also found that GRP78 was upregulated following treatment of the cells with nerve growth factor (NGF), despite NGF promoting cell viability [6,7]. This result suggests that GRP78 may serve as a functional protein in ER stress prevention, as well as a marker of ER stress.…”

mentioning

confidence: 76%

Epigenetic Regulation by Bisphenol A as a Neuronal Morphogen

Matsuura¹,

Yamazoe²,

Maruoka³

et al. 2017

J Bioengineer & Biomedical Sci

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EditorialSynthetic compounds are having epigenetic or cellular reprogramming impact which is an established truth. Commercial use of such synthetic compounds should be analyzed for health impact on human being before redundant use, especially related to food items. Bisphenol A (BPA) is one such compound which major used in the plastic industry and also for generation of epoxy compounds. There is an abundant use of this compound in packaging industry which includes canning food items. Therefore, thorough investigation is required regarding the impact of the compound on our health. Literature evidence is available related to the harmful effect of Bisphenol A, which generally acts as endocrine disruptors. Moreover, impact of BPA on male and female reproduction, neurological and behavioral issues have been proved earlier. It was found to have carcinogenic activity on human. Such impact is done generally through alteration of the epigenetic regulation of the DNA methylation. Endocrine disrupting chemicals (EDCs) promote a female-inducing phenotype in organs comprised of genital cells. Examples include miniaturized male genitalia and uterine cell death. The effects of EDCs are speculated to be due to their action as female-determinative factors through inhibition of endogenous male hormone receptors. Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that can cross the brain-brood barrier (BBB) due to its hydrophobic character [1], and thus, neurons or glial cells can be affected in a BPA-specific manner. We have found that EDC which involves alkylphenol group as same as BPA can cause apoptosis in PC12 cells [2]. This mechanism was classified as endoplasmic stress (ER)-mediated apoptosis, due to involvement of accumulation of unfolded proteins and upregulation of glucose-regulated protein 78 (GRP78), a marker of ER stress [3]. In addition, an ordinary apoptosis mechanism was also present [4,5]. We also found that GRP78 was upregulated following treatment of the cells with nerve growth factor (NGF), despite NGF promoting cell viability [6,7]. This result suggests that GRP78 may serve as a functional protein in ER stress prevention, as well as a marker of ER stress. In addition to functional prevention of ER stress-mediated apoptosis, NGF promotes neurite extension in PC12 cells [8]. This phenomenon is necessary for physiological development of the embryo and preservation of mature neurons. Surprisingly, we found that BPA mimicked the function of NGF, suggesting that endogenous hormonal ligands are inhibited by BPA. A morphological analysis showed that the shape of BPA-treated cells was the same as that of forskolin-treated cells (manuscript in preparation). Forskolin promotes neuronal differentiation via the PKA-CREB pathway, in which PKA activated by forskolin phosphorylates CREB, which then binds to CRE sites in various gene promoters (manuscript in preparation). This process also involves specific acetylation of histones, which also induces the expression of nur77 gene, one of the immediate early gene (manu...

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“…After incubation for 16 h, cells were either left untreated or were treated with 5 μM of K-350 for 0, 1, 2 or 4 h. Cells were then lysed in a lysis buffer containing 50 mM TrisHCl (pH7.8), 150 mM NaCl, 1% sodium dodecylsulfate (SDS), 1 mM ethylenediaminetetraacetic acid (EDTA), 1 mM phenylmethylsulfonyl fluoride (PMSF), 2 µg/ml leupeptin, 2µg/ml of aprotinin, 1 mM Na 3 VO 4 , and 10mM sodium butyrate [21]. Cell lysates (30 µg of protein per lane) were loaded on a sodium dodecylsulfate-polyacrylamide (SDS-PAGE) gel.…”

Section: Immunoblot Analysismentioning

confidence: 99%

New Orally Bioavailable 2-aminobenzamide-type Histone Deacetyase Inhibitor Promotes Neurite Outgrowth via histone H3 Modification in PC12 cells: a Possible Therapeutic Candidate for Neuronal Diseases

Maruoka¹,

Hosokawa²

2011

J Bioengineer & Biomedical Sci

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NGF-induced phosphatidylinositol 3-kinase signaling pathway prevents thapsigargin-triggered ER stress-mediated apoptosis in PC12 cells

Cited by 30 publications

References 17 publications

Calpain and caspase processing of caspase-12 contribute to the ER stress-induced cell death pathway in differentiated PC12 cells

Calpain and caspase processing of caspase-12 contribute to the ER stress-induced cell death pathway in differentiated PC12 cells

Epigenetic Regulation by Bisphenol A as a Neuronal Morphogen

New Orally Bioavailable 2-aminobenzamide-type Histone Deacetyase Inhibitor Promotes Neurite Outgrowth via histone H3 Modification in PC12 cells: a Possible Therapeutic Candidate for Neuronal Diseases

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