Cell death: protein misfolding and neurodegenerative diseases

Nakamura, Tomohiro; Lipton, Stuart A.

doi:10.1007/s10495-008-0301-y

Cited by 165 publications

(109 citation statements)

References 172 publications

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“…S8). In relation to this scenario, our study is under way to clarify a possible regulatory role of CIB1 in the activation of ASK1-JNK signaling processes initiated by NMDA signaling, which triggers both Ca 2ϩ influx and ROS production in neurons in the brain (31).…”

Section: Discussionmentioning

confidence: 99%

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

Yoon¹,

Cho²,

Lee³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Calcium and integrin binding protein 1 (CIB1) is a Ca 2+ -binding protein of 22 kDa that was initially identified as a protein that interacts with integrin α IIb . Although it interacts with various proteins and has been implicated in diverse cellular functions, the molecular mechanism by which CIB1 regulates intracellular signaling networks has remained unclear. We now show that, by targeting apoptosis signal-regulating kinase 1 (ASK1), CIB1 negatively regulates stress-activated MAPK signaling pathways. CIB1 was thus shown to bind to ASK1, to interfere with the recruitment of TRAF2 to ASK1, and to inhibit the autophosphorylation of ASK1 on threonine-838, thereby blocking ASK1 activation. Furthermore, CIB1 mitigated apoptotic cell death initiated either by TNF-α in breast cancer MCF7 cells or by 6-hydroxydopamine (6-OHDA) in dopaminergic cells. Ca 2+ influx induced by membrane depolarization reversed the inhibitory effect of CIB1 on 6-OHDA-induced ASK1 activation and cell death in dopaminergic neurons. These observations thus suggest that CIB1 functions as a Ca 2+ -sensitive negative regulator of ASK1-mediated signaling events.

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Section: Discussionmentioning

confidence: 99%

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

Yoon¹,

Cho²,

Lee³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…55 The current study showed that the expression of ER stress markers GRP78 (protein and mRNA) and c-Jun mRNA increased significantly in the MCDD group, whereas the expression of all of them decreased markedly after changing the diet. Another ER stress-related molecule, PDI, 30,31 showed similar behavior (Figure 6d and e). Thus, ER stress may be a key factor in MCDD-induced fatty liver fibrosis.…”

Section: Discussionmentioning

confidence: 63%

“…In addition, PDI, an ER-residing protein that catalyzes protein folding and thiol-disulfide interchange reactions, 30,31 was markedly induced in group M compared with groups C and R (Figure 6d). …”

Section: Involvement Of Er Stress In Fibrosis Of Steatohepatitis and mentioning

confidence: 99%

Reversibility of fibrosis, inflammation, and endoplasmic reticulum stress in the liver of rats fed a methionine–choline-deficient diet

Ogawa

Kawada

2010

Laboratory Investigation

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Fatty liver disease has become a health problem related to metabolic syndrome worldwide, although its molecular pathogenesis requires further study. It is also unclear whether advanced fibrosis of steatohepatitis will regress when diet is controlled. The aim of this study was to investigate whether the resolution of fibrosis occurs in steatohepatitis induced by a methionine-choline-deficient diet (MCDD). Manifestation of endoplasmic reticulum (ER) stress in this model was also studied. Nonalcoholic steatohepatitis with advanced fibrosis was induced in rats by feeding them an MCDD for 10 weeks. Instead of MCDD, a methionine-choline control diet (CD) was given for the last 2 weeks to the experimental group. Fibrosis and inflammation were determined by tissue staining. Protein and gene expressions were determined by immunoblotting and quantitative reverse transcription-PCR (RT-PCR), respectively. Expressions of caspase-7, caspase-12, glucose-regulated protein 78 (GRP78), and protein disulfide isomerase were evaluated to clarify the presence of ER stress. Changing the diet from MCDD to CD triggered the reduction of fat in hepatocytes, a decrease in inflammatory gene expression and oxidative stress, and regression of fibrosis accompanied by the disappearance of activated stellate cells and macrophages. Immunohistochemistry, immunoblotting, and RT-PCR analysis all indicated the occurrence of ER stress in steatohepatitis, while it recovered immediately after changing the diet from MCCD to CD. The ratio of hepatocyte proliferation/apoptotis increased significantly during the recovery stage. This simple experiment clearly shows that changing the diet from MCDD to a normal diet (CD) triggers the resolution of hepatic inflammatory and fibrotic reactions and hepatocyte apoptosis, suggesting that MCDD-induced steatohepatitis is also reversible. ER stress appears and disappears in association with the generation and regression of steatohepatitis, respectively, with fibrosis.

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“…Notably, NOS activation may increase the production of the rate-limiting enzyme for glutathione synthesis and of genes involved in antioxidant defence [41]. Similarly, NO has a dual role in the regulation of neuronal cell survival, being neuroprotective through Snitrosylation of NMDA receptors, and yet neurodestructive by the formation of peroxynitrite [42]. The dual role of NO in the regulation of beta cell survival is also demonstrated by its opposite effects on ER stress.…”

Section: Discussionmentioning

confidence: 99%

Neuronal nitric oxide synthase protects the pancreatic beta cell from glucolipotoxicity-induced endoplasmic reticulum stress and apoptosis

et al. 2010

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Aims/hypothesis Cytokines stimulate nitric oxide production in pancreatic beta cells, leading to endoplasmic reticulum (ER) stress and apoptosis. Treatment of beta cells with glucose and NEFA induces nitric oxide synthase (NOS) as well as ER stress. However, the role of NO in glucolipotoxicity-induced ER stress in beta cells is not clear. Methods We studied the effect of high glucose and palmitate levels on NOS isoform production in rat and Psammomys obesus islets and in insulinoma-1E beta cells. The effects of neuronal NOS (nNOS) inhibition by small interfering RNA or by N ω -nitro-L-arginine methyl ester (L-NAME) on beta cell function, ER stress and apoptosis under conditions of glucolipotoxicity were investigated. Results Overnight incubation of rat and P. obesus islets at 22.2 mmol/l glucose with 0.5 mmol/l palmitate induced the production of nNOS but not inducible NOS (iNOS), in contrast with the robust stimulation of iNOS by cytokines. NOS inhibition by L-NAME did not prevent the decrease in glucose-stimulated insulin secretion and proinsulin biosynthesis or the depletion of islet insulin content observed under conditions of glucolipotoxicity. Moreover, treatment of beta cells with palmitate and L-NAME together resulted in marked activation of the IRE1α and PERK pathways of the unfolded protein response. This was associated with increased JNK phosphorylation and apoptosis in islets and beta cells. Moreover, partial nNos knockdown increased JNK phosphorylation and CHOP production, leading to apoptosis. Conclusions/interpretation In beta cells subjected to glucolipotoxic conditions, chronic inhibition of NOS exacerbates ER stress and activates JNK. Therefore, induction of nNOS is an adaptive response to glucolipotoxicity that protects beta cells from stress and apoptosis.

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Cell death: protein misfolding and neurodegenerative diseases

Cited by 165 publications

References 172 publications

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

Reversibility of fibrosis, inflammation, and endoplasmic reticulum stress in the liver of rats fed a methionine–choline-deficient diet

Neuronal nitric oxide synthase protects the pancreatic beta cell from glucolipotoxicity-induced endoplasmic reticulum stress and apoptosis

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Cell death: protein misfolding and neurodegenerative diseases

Cited by 165 publications

References 172 publications

CIB1 functions as a Ca 2+ -sensitive modulator of stress-induced signaling by targeting ASK1

CIB1 functions as a Ca 2+ -sensitive modulator of stress-induced signaling by targeting ASK1

Reversibility of fibrosis, inflammation, and endoplasmic reticulum stress in the liver of rats fed a methionine–choline-deficient diet

Neuronal nitric oxide synthase protects the pancreatic beta cell from glucolipotoxicity-induced endoplasmic reticulum stress and apoptosis

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CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1

CIB1 functions as a Ca ²⁺ -sensitive modulator of stress-induced signaling by targeting ASK1