Oxygen–Glucose Deprivation (OGD) Modulates the Unfolded Protein Response (UPR) and Inflicts Autophagy in a PC12 Hypoxia Cell Line Model

Hypoxia is the lack of sufficient oxygenation of tissue, imposing severe stress upon cells. It is a major feature of many pathological conditions such as stroke, traumatic brain injury, cerebral hemorrhage, perinatal asphyxia and can lead to cell death due to energy depletion and increased free radi...

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Published in:Cellular and molecular neurobiology 2016-07, Vol.36 (5), p.701-712
Main Authors: Vavilis, Theofanis, Delivanoglou, Nikoleta, Aggelidou, Eleni, Stamoula, Eleni, Mellidis, Kyriakos, Kaidoglou, Aikaterini, Cheva, Angeliki, Pourzitaki, Chryssa, Chatzimeletiou, Katerina, Lazou, Antigone, Albani, Maria, Kritis, Aristeidis
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Autophagy - physiology
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell Hypoxia
Cell Survival
Endoplasmic Reticulum Chaperone BiP
Glucose - metabolism
Neurobiology
Neurons - metabolism
Neurosciences
Original Research
Oxygen - metabolism
PC12 Cells
Rats
Unfolded Protein Response - physiology
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Summary:Hypoxia is the lack of sufficient oxygenation of tissue, imposing severe stress upon cells. It is a major feature of many pathological conditions such as stroke, traumatic brain injury, cerebral hemorrhage, perinatal asphyxia and can lead to cell death due to energy depletion and increased free radical generation. The present study investigates the effect of hypoxia on the unfolded protein response of the cell (UPR), utilizing a 16-h oxygen–glucose deprivation protocol (OGD) in a PC12 cell line model. Expression of glucose-regulated protein 78 (GRP78) and glucose-regulated protein 94 (GRP94), key players of the UPR, was studied along with the expression of glucose-regulated protein 75 (GRP75), heat shock cognate 70 (HSC70), and glyceraldehyde 3-phosphate dehydrogenase, all with respect to the cell death mechanism(s). Cells subjected to OGD displayed upregulation of GRP78 and GRP94 and concurrent downregulation of GRP75. These findings were accompanied with minimal apoptotic cell death and induction of autophagy. The above observation warrants further investigation to elucidate whether autophagy acts as a pro-survival mechanism that upon severe and prolonged hypoxia acts as a concerted cell response leading to cell death. In our OGD model, hypoxia modulates UPR and induces autophagy.
ISSN:0272-4340
1573-6830
1573-6830
DOI:10.1007/s10571-015-0250-2