Abstract:
PURPOSE:Proteasome inhibition induces endoplasmic reticulum (ER) stress and compensatory autophagy to relieve ER stress. Disturbance of intracellular calcium homeostasis can lead to ER stress and alter the autophagy process. It has been suggested that inhibition of the proteasome disrupts intracellular calcium homeostasis. However, it is unknown if intracellular calcium affects proteasome inhibitor-induced ER stress and autophagy. METHODS:Human colon cancer HCT116 Bax positive and negative cell lines were treated with MG132, a proteasome inhibitor. BAPTA-AM, a cell permeable free calcium chelator, was used to modulate intracellular calcium levels. Autophagy and cell death were determined by fluorescence microscopy and immunoblot analysis. RESULTS:MG132 increased intracellular calcium levels in HCT116 cells, which was suppressed by BAPTA-AM. MG132 suppressed proteasome activity independent of Bax and intracellular calcium levels in HCT116 cells. BAPTA-AM inhibited MG132-induced cellular vacuolization and ER stress, but not apoptosis. MG132 induced autophagy with normal autophagosome-lysosome fusion. BAPTA-AM seemed not to affect autophagosome-lysosome fusion in MG132-treated cells but further enhanced MG132-induced LC3-II levels and GFP-LC3 puncta formation, which was likely via impaired lysosome function. CONCLUSIONS:Blocking intracellular calcium by BAPTA-AM relieved MG132-induced ER stress, but it was unable to rescue MG132-induced apoptosis, which was likely due to impaired autophagic degradation.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Williams JA,Hou Y,Ni HM,Ding WXdoi
10.1007/s11095-013-1139-8subject
Has Abstractpub_date
2013-09-01 00:00:00pages
2279-89issue
9eissn
0724-8741issn
1573-904Xjournal_volume
30pub_type
杂志文章abstract:PURPOSE:Permeation studies, with near infrared (NIR) light and anti-aggregation antibody formulation, were used to investigate the in vitro permeation of bevacizumab, ranibizumab and aflibercept through human sclera. METHODS:A vertical, spherical Franz cell diffusion apparatus was used for this scleral tissue permeati...
journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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journal_title:Pharmaceutical research
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更新日期:2007-06-01 00:00:00
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更新日期:2009-06-01 00:00:00
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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更新日期:2000-10-01 00:00:00
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journal_title:Pharmaceutical research
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doi:10.1023/a:1015855622459
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更新日期:2017-01-01 00:00:00
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journal_title:Pharmaceutical research
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更新日期:2006-07-01 00:00:00
abstract::Interogan variation in tissue distribution of weakly basic drugs such as quinidine, propranolol, and imipramine was investigated as a function of binding to phosphatidylserine (PhS) in tissues. Tissue distributions of these drugs were determined using 10 different tissues at a steady-state plasma concentration and wer...
journal_title:Pharmaceutical research
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doi:10.1023/a:1015935031933
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02901-0
更新日期:2020-08-13 00:00:00
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journal_title:Pharmaceutical research
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doi:10.1023/a:1015960815578
更新日期:1990-08-01 00:00:00
abstract:PURPOSE:The aim of this study was to identify the dominant factors affecting the stability of nanoemulsions, using artificial neural networks (ANNs). METHODS:A nanoemulsion preparation of budesonide containing polysorbate 80, ethanol, medium chain triglycerides and saline solution was designed, and the particle size o...
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doi:10.1007/s11095-009-0004-2
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更新日期:2007-07-01 00:00:00
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更新日期:1994-12-01 00:00:00
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更新日期:2007-11-01 00:00:00
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更新日期:2006-02-01 00:00:00
abstract:PURPOSE:Previous studies by other investigators have shown an enhancement of mitomycin C (MMC) activity at acidic extracellular pH (pHe) in monolayer cultures of human cells. The goal of the present study was to determine if the efficacy of intravesical MMC therapy in patients treated for superficial bladder cancer can...
journal_title:Pharmaceutical research
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更新日期:1996-12-01 00:00:00
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journal_title:Pharmaceutical research
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更新日期:2017-10-01 00:00:00
abstract::The molecular environment of sucrose and mineral oil within sucrose and mineral oil solid state emulsions was investigated by NMR techniques. The 13C and 1H chemical shifts of sucrose and mineral oil to those observed in solid state emulsions (comprised of sucrose and mineral oil) were equivalent, indicating that the ...
journal_title:Pharmaceutical research
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更新日期:1994-09-01 00:00:00
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更新日期:2001-09-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2005-02-01 00:00:00
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更新日期:1998-06-01 00:00:00