Please use this identifier to cite or link to this item:
|Title:||Acute hypoxia induces apoptosis of pancreatic β-cell by activation of the unfolded protein response and upregulation of CHOP||Authors:||Zheng, X.
Gupta Sunkari, V.
|Issue Date:||Jun-2012||Citation:||Zheng, X., Zheng, X., Wang, X., Ma, Z., Gupta Sunkari, V., Botusan, I., Takeda, T., Björklund, A., Inoue, M., Catrina, S.-B., Brismar, K., Poellinger, L., Pereira, T.S. (2012-06). Acute hypoxia induces apoptosis of pancreatic β-cell by activation of the unfolded protein response and upregulation of CHOP. Cell Death and Disease 3 (6) : e322-. ScholarBank@NUS Repository. https://doi.org/10.1038/cddis.2012.66||Abstract:||The success of pancreatic β-cells transplantation to treat type 1 diabetes has been hindered by massive β-cell dysfunction and loss of β-cells that follows the procedure. Hypoxia-mediated cell death has been considered one of the main difficulties that must be overcome for transplantation to be regarded as a reliable therapy. Here we have investigated the mechanisms underlying b-cell death in response to hypoxia (1% O 2). Our studies show that mouse insulinoma cell line 6 (Min6) cells undergo apoptosis with caspase-3 activation occurring as early as 2 h following exposure to hypoxia. Hypoxia induces endoplasmic reticulum stress in Min6 cells leading to activation of the three branches of the unfolded protein response pathway. In response to hypoxia the pro-apoptotic transcription factor C/EBP homologous protein (CHOP) is upregulated. The important role of CHOP in the apoptotic process was highlighted by the rescue of Min6 cells from hypoxia-mediated apoptosis observed in CHOP-knockdown cells. Culturing isolated pancreatic mouse islets at normoxia showed intracellular hypoxia with accumulation of hypoxiainducible factor-1α and upregulation of CHOP, the latter one occurring as early as 4 h after isolation. Finally, we observed that pancreatic islets of type 2 db/db diabetic mice were more hypoxic than their counterpart in normoglycemic animals. This finding indicates that hypoxia-mediated apoptosis may occur in type 2 diabetes. © 2012 Macmillan Publishers Limited All rights reserved.||Source Title:||Cell Death and Disease||URI:||http://scholarbank.nus.edu.sg/handle/10635/114987||ISSN:||20414889||DOI:||10.1038/cddis.2012.66|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jun 29, 2020
WEB OF SCIENCETM
checked on Jun 22, 2020
checked on Jun 27, 2020
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.