Caspases involved in ER stress-mediated cell death

Momoi, Takashi

doi:10.1016/j.jchemneu.2004.05.008

Cited by 190 publications

(149 citation statements)

References 43 publications

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“…Recent studies suggest ER as another subcellular center implicated in apoptotic execution. Many stimuli including alterations in calcium homeostasis, production of reactive oxygen species (ROS) and accumulation of unfolded proteins in the ER can cause ER stress [9,19] and prolonged ER Fig. 7.…”

Section: Discussionmentioning

confidence: 99%

“…The ER plays an important role in maintenance of intracellular calcium homeostasis, protein synthesis, posttranslational modifications, and proper folding of proteins as well as their sorting and trafficking. Many stimuli, including alterations in calcium homeostasis and accumulation of unfolded proteins in the ER, can cause stress [9,19] and prolonged ER stress will lead to apoptosis via caspase-4 dependent pathway. Crosstalk with the two well-characterized pathways also exists since ER stress can also activate caspase-9 by releasing cytochrome c from mitochondria to cytosol and activate caspase-8 [19,20].…”

Section: Introductionmentioning

confidence: 99%

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Trichosanthin induced apoptosis in HL-60 cells via mitochondrial and endoplasmic reticulum stress signaling pathways

Xia

Yao

et al. 2007

Biochimica et Biophysica Acta (BBA) - General Subjects

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Trichosanthin (TCS), a traditional Chinese medicine, exerts antitumor activities by inducing apoptosis in many different tumor cell lines. However, the mechanisms remain obscure. The present study focused on various caspase pathways that may be involved in TCS-induced apoptosis in leukemia HL-60 cells. Key caspases in both intrinsic and extrinsic pathways including caspase-8, -9 and -3 were activated upon TCS treatment. Additionally, TCS treatment induced upregulation of BiP and CHOP and also activated caspase-4, which for the first time strongly supported the involvement of endoplasmic reticulum stress pathway in TCS-induced apoptosis. Interestingly, although caspase-8 was activated, Fas/Fas ligand pathway was not involved as evidenced by a lack of induction of Fas or Fas ligand and a lack of inhibitory effect of anti-Fas blocking antibody on TCS-induced apoptosis. Instead, caspase-8 was activated in a caspase-9 and -4 dependent manner. The involvement of mitochondria was demonstrated by the reduction of mitochondrial membrane potential and release of cytochrome c and Smac besides the activation of caspase-9. Further investigation confirmed that caspase-3 was the major executioner caspase downstream to caspase-9, -4 and -8. Taken together, our results suggested that TCS-induced apoptosis in HL-60 cells was mainly mediated by mitochondrial and ER stress signaling pathways via caspase-3.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Trichosanthin induced apoptosis in HL-60 cells via mitochondrial and endoplasmic reticulum stress signaling pathways

Xia

Yao

et al. 2007

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…However, excessively strong or long-time ER stress can lead cell apoptosis, namely ER stress-mediated cell death. 13 Recently, ER stress-mediated apoptosis pathway has been proven to play a crucial role in the degenerative pathophysiology of neurodegenerative disorders, [14][15][16][17][18] retinitis pigmentosa, and other eye diseases. [19][20][21][22] Masamitsu Shimazawa and colleagues 23,24 found that ER-stress played a pivotal role in RGC death.…”

Section: Introductionmentioning

confidence: 99%

Expression of two endoplasmic reticulum stress markers, GRP78 and GADD153, in rat retinal detachment model and its implication

Liu

Qian

Wang

et al. 2009

Eye

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Purpose To investigate the expression of endoplasmic reticulum (ER) stress-related genes, glucose-regulated protein 78 (GRP78) and growth arrest DNA damage-inducible gene 153 (GADD153)/CPEBP homologous protein (CHOP), in rat retinal detachment (RD) model. Materials and methods At various time points after RD, the apoptosis of retinal cells was detected by TdT-mediated fluorescein-16-dUTP nick-end labelling (TUNEL) assay; GRP78 and GADD153 mRNA levels were detected by reverse transcription (RT)-PCR; proteins were detected by western blotting analysis; protein distributions in the retinal cells were observed by immunofluorescence using laser-scanning confocal microscope. Results After RD, the apoptosis was peaked on 2-4 d and then dropped down. The GRP78 mRNA and GADD153 mRNA levels in RD groups on 0.5, 1, 2, and 4 d were all significantly higher than those in the control group (Po0.05). The expression of GRP78 mRNA peaked on 1-2 d after RD. Expression of GRP78 protein was significantly higher than that in the normal control group on 0.5, 1, 2, 4, 8, 16, and 32 d after RD (Po0.05). The expression of GRP78 protein was observed in all the layers of retina in the RD groups, and peaked on 8, 16, and 32 d. The expression of GADD153 protein, mostly in photoreceptor layers, was significantly higher than that in the control group on 0.5, 1, 2, and 4 d after RD (Po0.05). Conclusions ER stress-related markers, GRP78 and GADD153, are elevated after RD.The elevation of GADD153 is in parallel with the post-RD apoptosis of retinal cells, suggesting that ER stress-mediated death is likely to be activated after RD and involved in post-RD vision loss.

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“…15 However, if the amount of unfolded and malfolded proteins exceeds the capacity of the ERAD system, the proteins start to aggregate in the ER and trigger ER-stress-mediated cell death with caspase-12 activation, a caspase specifically localized at ER. 16,17 The cytoplasmic aggregates of malfolded proteins such as polyQ also stimulate ER stress signals and induce ER-stress-mediated cell death with caspase-12 activation in mouse cells, presumably by the accumulation of unfolded proteins in the ER due to the inhibition of ERAD and retrotranslocation. 18,19 Here, we show that Rap inhibits the polyQ-induced ERstress-mediated cell death with caspase-12 activation.…”

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confidence: 99%

ER stress (PERK/eIF2α phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation

et al. 2006

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Expanded polyglutamine 72 repeat (polyQ72) aggregates induce endoplasmic reticulum (ER) stress-mediated cell death with caspase-12 activation and vesicular formation (autophagy). We examined this relationship and the molecular mechanism of autophagy formation. Rapamycin, a stimulator of autophagy, inhibited the polyQ72-induced cell death with caspase-12 activation. PolyQ72, but not polyQ11, stimulated Atg5-Atg12-Atg16 complex-dependent microtubule-associated protein 1 (MAP1) light chain 3 (LC3) conversion from LC3-I to -II, which plays a key role in autophagy. The eucaryotic translation initiation factor 2 a (eIF2a) A/A mutation, a knock-in to replace a phosphorylatable Ser 51 with Ala 51 , and dominant-negative PERK inhibited polyQ72-induced LC3 conversion. PolyQ72 as well as ER stress stimulators upregulated Atg12 mRNA and proteins via eIF2a phosphorylation. Furthermore, Atg5 deficiency as well as the eIF2a A/A mutation increased the number of cells showing polyQ72 aggregates and polyQ72-induced caspase-12 activation. Thus, autophagy formation is a cellular defense mechanism against polyQ72-induced ER-stress-mediated cell death by degrading polyQ72 aggregates, with PERK/eIF2a phosphorylation being involved in polyQ72-induced LC3 conversion.

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Caspases involved in ER stress-mediated cell death

Cited by 190 publications

References 43 publications

Trichosanthin induced apoptosis in HL-60 cells via mitochondrial and endoplasmic reticulum stress signaling pathways

Trichosanthin induced apoptosis in HL-60 cells via mitochondrial and endoplasmic reticulum stress signaling pathways

Expression of two endoplasmic reticulum stress markers, GRP78 and GADD153, in rat retinal detachment model and its implication

ER stress (PERK/eIF2α phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation

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