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Hypoxia protects neuronal cells from human prion protein fragment‐induced apoptosis
Author(s) -
Seo JaeSuk,
Seol JaeWon,
Moon MyungHee,
Jeong JaeKyo,
Lee YouJin,
Park SangYouel
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06496.x
Subject(s) - apoptosis , protein kinase b , hypoxia (environmental) , biology , programmed cell death , microbiology and biotechnology , gene isoform , pi3k/akt/mtor pathway , neurodegeneration , cell culture , cell , chemistry , biochemistry , gene , pathology , medicine , disease , oxygen , genetics , organic chemistry
J. Neurochem. (2010) 112 , 715–722. Abstract Prion diseases are neurodegenerative disorders characterized by the accumulation of an abnormal isoform of the prion protein PrP Sc . Human prion protein fragment, PrP (106–126) (prion protein peptide 106–126), may contain most of the pathological features associated with PrP Sc . Hypoxic conditions elicit cellular responses adaptively designed to improve cell survival and have an important role in the process of cell survival. We investigate the effects of hypoxia on PrP (106–126)‐induced apoptosis in the present study. Human neuroblastoma and glioblastoma cells were incubated with varied doses of PrP (106–126) under both normoxic or hypoxic conditions, in order to determine the regulatory effects of hypoxia on PrP (106–126)‐induced apoptosis. The results indicate that hypoxia protects neuronal cells against PrP (106–126)‐induced cell death by activating the Akt signal, which is inactivated by prion proteins, and inhibiting PrP (106–126)‐induced caspase 3 activation. Low oxygen conditions increase the Bcl‐2 protein, which is associated with anti‐apoptotic signals, and recover the PrP (106–126)‐induced reduction in mitochondrial transmembrane potential. This study demonstrates that hypoxia inhibits PrP (106–126)‐induced neuron cell death by regulating Akt and Akt‐related signaling, and it also suggests that prion‐related neuronal damage and disease may be regulated by hypoxia or by hypoxic‐inducing genes.