Please use this identifier to cite or link to this item:
|Title:||Activation of caspase-2 mediates the apoptosis induced by GTP-depletion in insulin-secreting (HIT-T15) cells||Authors:||Huo, J.
|Issue Date:||2002||Citation:||Huo, J., Luo, R.-H., Metz, S.A., Li, G. (2002). Activation of caspase-2 mediates the apoptosis induced by GTP-depletion in insulin-secreting (HIT-T15) cells. Endocrinology 143 (5) : 1695-1704. ScholarBank@NUS Repository. https://doi.org/10.1210/en.143.5.1695||Abstract:||This study investigated the possible involvement of a specific caspase(s) (a family of aspartate-specific cysteine proteases) in programmed cell death of islet β-cells due to sustained GTP depletion. Treatment (up to 48 h) with 3 μg/ml mycophenolic acid (MPA), which specifically depletes intracellular guanine nucleotides, reduced cell-cycle progression from G1 phase into S and G2/M phases (as assessed by flow cytometry) and, subsequently, induced apoptosis of HIT-15 cells (transformed pancreatic β-cells). The latter was accompanied by a marked increase of caspase-2 activity (+343%) and moderate activation of caspase-9 (+150%) and caspase-3 (+145%). Importantly, only caspase-2 activation preceded induction ofapoptosis. There was no change in activity of caspase-1, -4, -5, -6, and -8. Release of the mitochondrial protein cytochrome c into cytosol was also observed at a late stage. Cotreatment of cells with a permeable pan-caspase inhibitor (Z-VAD-FMK) blocked GTP depletion-induced cell death in a dose-dependent manner. A specific caspase-2 inhibitor (Z-VDVAD-FMK), but not a caspase-3 inhibitor (DEVD-CHO), was also capable of restoring cell viability. Interestingly, activation of caspase-2 leads to caspase-3 activation because the caspase-2 inhibitor abrogated caspase-3 activity. Our results indicate that, while activation of multiple caspases are involved in the execution phase of GTP depletion-induced apoptosis, caspase-2 appears to play the major role in the initiation of this program. This study revealed a novel, caspase-2 mediated form of apoptosis that may be consequent to impaired mitogenesis.||Source Title:||Endocrinology||URI:||http://scholarbank.nus.edu.sg/handle/10635/112779||ISSN:||00137227||DOI:||10.1210/en.143.5.1695|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
WEB OF SCIENCETM
checked on Oct 11, 2019
checked on Oct 11, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.