α-Tocopherol-mediated caspase-3 up-regulation enhances susceptibility to apoptotic stimuli

Miyoshi, Noriyuki; Naniwa, Kisa; Kumagai, Takeshi; Uchida, Koji; Osawa, Toshihiko; Nakamura, Yoshimasa

doi:10.1016/j.bbrc.2005.06.113

Cited by 16 publications

(12 citation statements)

References 28 publications

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“…Both pro-caspase-3 and caspase-3 could be up-regulated by apoptotic stimuli (19). It was found that silibinin induced apoptosis by elevated expression of both inactive pro-caspase-3 and active caspase-3 in HT1080 cells either cultured in 10% FBS ( Fig.…”

Section: Apoptosis Was Induced In Silibinin-treated Ht1080 Cells Cultmentioning

confidence: 88%

Silibinin Induced Autophagic and Apoptotic Cell Death in HT1080 Cells Through a Reactive Oxygen Species Pathway

Duan

Jin

et al. 2010

J Pharmacol Sci

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Abstract. Hepatoprotectant silibinin has anticancer and chemo-preventive effects. In this study, silibinin showed significant inhibitory effect on human fibroblast HT 1080 cell growth cultured in media containing 10% fetal bovine serum or in serum free media, and in the latter case, silibinin exerted a more significant effect. Silibinin induced autophagy at 12 h, confirmed by monodansylcadervarine (MDC) staining, up-regulation of Beclin 1 (initiation factor for autophagosome formation), and conversion of LC3 I to LC3 II (autophagosome marker). It also induced apoptosis at 24 h, proved by observation of apoptotic body and activation of caspase-3. 3-Methyladenine (3-MA) inhibited silibinin-induced autophagy and promoted cell survival, suggesting that autophagy enhanced silibinin-induced apoptosis in HT1080 cells. Silibinin generated reactive oxygen species (ROS) in HT1080 cells, and the ROS scavenger N -acetylcysteine (NAC) reversed the cytotoxicity of silibinin, resulting in cell survival by inhibition of autophagic and apoptotic pathways. Application of specific antioxidants demonstrated that H 2 O 2 was a major factor in silibinin-induced ROS since the H 2 O 2 scavenger catalase reduced both autophagy and cell death. O 2• − also contributed to silibinin-induced cell death.

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Section: Apoptosis Was Induced In Silibinin-treated Ht1080 Cells Cultmentioning

confidence: 88%

Silibinin Induced Autophagic and Apoptotic Cell Death in HT1080 Cells Through a Reactive Oxygen Species Pathway

Duan

Jin

et al. 2010

J Pharmacol Sci

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“…The antioxidant activity of a-tocopherol in preventing free radical-initiated peroxidative tissue damage is accepted by most investigators and is believed to be the primary free radical scavenger in mammalian cell membrane (Rose and Bode 1993;Droge 2002). The direct action of a-tocopherol has been attributed to its ability in functioning as a lipid-based free radical chain-breaking molecule, which protects the organism against these radicals (Miyoshi et al 2005;Traber and Atkinson 2007) and, thereby, prevents from apoptosis and necrosis (Ikeda et al 2003;Kang et al 2006).…”

Section: Introductionmentioning

confidence: 94%

Vitamins E and D3 Attenuate Demyelination and Potentiate Remyelination Processes of Hippocampal Formation of Rats Following Local Injection of Ethidium Bromide

et al. 2009

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Cognitive deficits have been observed in patients with multiple sclerosis (MS) due to hippocampal insults. Antioxidant vitamins D and E are suggested for patients suffering from neurodegenerative diseases like MS, while their mechanisms of action are not well understood. Here, we have tried to study the effects of these vitamins on demyelination, cell death, and remyelination of rat hippocampus following local ethidium bromide (EB) injection. Animals received 100 mg/kg vitamin E or 5 microg/kg of vitamin D3 for 2, 7, or 28 days. The extent of demyelination, myelin staining intensity, and expression of myelin basic protein and caspase-3 were investigated using histological and immunoblotting verification. Administration of EB alone caused demyelination, cell death, and afterward an endogenous repair. Vitamins E and D3 reduced the EB-induced damage and increased the endogenous remyelination of hippocampus. Although the anti-apoptotic effect of these vitamins and protection against demyelination were predictable based on their antioxidant effect, our results indicated the positive effect of vitamins E and D3 on process of remyelination by endogenous progenitor cells and supported their possible therapeutic effects in the context of demyelinating diseases like MS.

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“…Caspases are pivotal mediators of apoptosis. Caspase-3 (previously called CPP32, Yama, apopain) is the major downstream protease in all apoptotic pathways [49]. Our studies observed that cathepsin L inhibitors could also reduce QA-induced activation of caspase-3 by inhibition NF-κB nuclear translocation and the expression of its target gene TP53.…”

Section: Discussionmentioning

confidence: 66%

Cathepsin L Plays a Role in Quinolinic Acid-Induced NF-Κb Activation and Excitotoxicity in Rat Striatal Neurons

et al. 2013

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The present study seeks to investigate the role of cathepsin L in glutamate receptor-induced transcription factor nuclear factor-kappa B (NF-κB) activation and excitotoxicity in rats striatal neurons. Stereotaxic administration of the N-methyl-d-aspartate (NMDA) receptor agonist Quinolinic acid (QA) into the unilateral striatum was used to produce the in vivo excitotoxic model. Co-administration of QA and the cathepsin L inhibitor Z-FF-FMK or 1-Naphthalenesulfonyl-IW-CHO (NaphthaCHO) was used to assess the contribution of cathepsin L to QA-induced striatal neuron death. Western blot analysis and cathepsin L activity assay were used to assess the changes in the levels of cathepsin L after QA treatment. Western blot analysis was used to assess the changes in the protein levels of inhibitor of NF-κB alpha isoform (IκB-α) and phospho-IκB alpha (p-IκBα) after QA treatment. Immunohistochemical analysis was used to detect the effects of Z-FF-FMK or NaphthaCHO on QA-induced NF-κB. Western blot analysis was used to detect the effects of Z-FF-FMK or NaphthaCHO on QA-induced IκB-α phosphorylation and degradation, changes in the levels of IKKα, p-IKKα, TP53, caspase-3, beclin1, p62, and LC3II/LC3I. The results show that QA-induced loss of striatal neurons were strongly inhibited by Z-FF-FMK or NaphthaCHO. QA-induced degradation of IκB-α, NF-κB nuclear translocation, up-regulation of NF-κB responsive gene TP53, and activation of caspase-3 was strongly inhibited by Z-FF-FMK or NaphthaCHO. QA-induced increases in beclin 1, LC3II/LC3I, and down-regulation of p62 were reduced by Z-FF-FMK or NaphthaCHO. These results suggest that cathepsin L is involved in glutamate receptor-induced NF-κB activation. Cathepsin L inhibitors have neuroprotective effects by inhibiting glutamate receptor-induced IκB-α degradation and NF-κB activation.

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α-Tocopherol-mediated caspase-3 up-regulation enhances susceptibility to apoptotic stimuli

Cited by 16 publications

References 28 publications

Silibinin Induced Autophagic and Apoptotic Cell Death in HT1080 Cells Through a Reactive Oxygen Species Pathway

Silibinin Induced Autophagic and Apoptotic Cell Death in HT1080 Cells Through a Reactive Oxygen Species Pathway

Vitamins E and D3 Attenuate Demyelination and Potentiate Remyelination Processes of Hippocampal Formation of Rats Following Local Injection of Ethidium Bromide

Cathepsin L Plays a Role in Quinolinic Acid-Induced NF-Κb Activation and Excitotoxicity in Rat Striatal Neurons

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