Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery
Publication Date : //
The role of Apaf-1, caspase-9, and bid proteins in etoposide- or paclitaxel-induced mitochondrial events during apoptosis.
Ectopic overexpression of Apaf-1 (2.5-fold) in human acute myelogenous leukemia HL-60 cells (HL-60/Apaf-1 cells) induced apoptosis and sensitized HL-60/Apaf-1 cells to etoposide- and paclitaxel-induced apoptosis (C. Perkins et al., Cancer Res., 58: 4561-4566, 1998). In this report, we demonstrate that in HL-60/Apaf-1 cells, the activity of caspase-9 and -3 induced by Apaf-1 overexpression was associated with a significant increase (5-fold) in the cytosolic accumulation of cytochrome c (cyt c), loss of mitochondrial membrane potential (deltapsim), and an increase in the reactive oxygen species. These were also associated with the processing of procaspase-8 and Bid (cytosolic, proapoptotic BH3 domain containing protein). Transient transfection of Apaf-1 into the Apaf-1-containing mouse embryogenic fibroblasts (MEFs; Apaf-1+/- MEFs) or Apaf-1-/- MEFs also induced the processing of procaspase-9 and procaspase-8, Bid cleavage, and apoptosis. These events were secondary to the activity of the downstream caspases induced by Apaf-1. This conclusion is supported by the observation that in HL-60/Apaf-1 cells, ectopic expression of dominant negative caspase-9, its inhibitory short isoform caspase-9b, or XIAP or treatment with the caspase inhibitor zVAD (50 microM) inhibited Apaf-1-induced caspase-8 and Bid cleavage, mitochondrial deltapsim, release of cyt c, and apoptosis. In contrast, a transient transfection of dominant negative caspase-8 or CrmA or exposure to caspase-8 inhibitor zIETD-fmk inhibited the processing of procaspase-8 and Bid but did not inhibit the cytosolic accumulation of cyt c in either the untreated HL-60/Apaf-1 cells or the etoposide-treated HL-60/Apaf-1 and HL-60/neo cells. These results indicate that Apaf-1 overexpression lowers the apoptotic threshold by activating caspase-9 and caspase-3. This triggers the mitochondrial deltapsim and cyt c release into the cytosol through a predominant mechanism other than cleavage of caspase-8 and/or Bid. This mechanism may involve a cytosolic mitochondrial permeability transition factor, which may be processed and activated by the downstream effector caspases, thereby completing an amplifying feedback loop, which triggers the mitochondrial events during apoptosis.
Authors : Perkins C L , Fang G , Kim C N , Bhalla K N ,
Related products :
52062 Aachen Deutschland
Support Karolina Elandt
Tel: +49 0241 40 08 90 86, +49 0241 95 78 94 78, +49 0241 40 08 90 86
Fax: (+49) 241 56 00 47 88
Logistic :0241 40 08 90 86
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
firstname.lastname@example.org | Gentaur | Gentaur
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123
Canada Montreal +15149077481
Ceská republika Praha +420246019719
Finland Helsset +358942419041
Magyarország Budapest +3619980547
US New York+17185132983
WP1313: Insulin Signaling
WP1315: IL-5 Signaling Pathway
WP1330: estrogen signalling
WP163: Cytoplasmic Ribosomal Proteins
WP2119: Interferon induced apoptosis
WP2414: Quercetin and Nf-kB/ AP-1 induced cell apoptosis
WP2435: Quercetin and Nf-kB/ AP-1 induced cell apoptosis
WP100: Glutathione metabolism
WP1016: Wnt Signaling Pathway
WP1032: NLR proteins
WP1039: Glutathione metabolism
WP104: Alanine and aspartate metabolism
WP1056: Complement and Coagulation Cascades
WP106: Alanine and aspartate metabolism
WP1071: Cytoplasmic Ribosomal Proteins
WP1082: Apoptosis Modulation by HSP70
WP1107: Mitochondrial LC-Fatty Acid Beta-Oxidation
WP1126: Tryptophan metabolism
WP1135: Wnt Signaling Pathway
WP1172: Complement and Coagulation Cascades
WP1187: Cytoplasmic Ribosomal Proteins
WP1199: Apoptosis Modulation by HSP70
Related Genes :
 Zerumbone, a ginger sesquiterpene, induces apoptosis and autophagy in human hormone-refractory prostate cancers through tubulin binding and crosstalk between endoplasmic reticulum stress and mitochondrial insult.
 Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells.
 Cdk2 acts upstream of mitochondrial permeability transition during paclitaxel-induced apoptosis.
 KSP inhibitor ARRY-520 as a substitute for Paclitaxel in Type I ovarian cancer cells.
 Epidermal growth factor receptor inhibitor (PD168393) potentiates cytotoxic effects of paclitaxel against androgen-independent prostate cancer cells.
 Induction of tumor necrosis factor by bryostatin 1 is involved in synergistic interactions with paclitaxel in human myeloid leukemia cells.
 Paclitaxel triggers cell death primarily via caspase-independent routes in the non-small cell lung cancer cell line NCI-H460.
 Caspase-8/FLICE functions as an executioner caspase in anticancer drug-induced apoptosis.
 The role of Apaf-1, caspase-9, and bid proteins in etoposide- or paclitaxel-induced mitochondrial events during apoptosis.
Enter catalog number :