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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1471-4159.2009.06496.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
SIRT1 Regulates Mitochondrial Damage in N2a Cells Treated with the Prion Protein Fragment 106-126 via PGC-1α-TFAM-Mediated Mitochondrial Biogenesis.
Int J Mol Sci
September 2024
National Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Mitochondrial damage is an early and key marker of neuronal damage in prion diseases. As a process involved in mitochondrial quality control, mitochondrial biogenesis regulates mitochondrial homeostasis in neurons and promotes neuron health by increasing the number of effective mitochondria in the cytoplasm. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates neuronal mitochondrial biogenesis and quality control in neurodegenerative diseases via deacetylation of a variety of substrates.
View Article and Find Full Text PDFAssessment of the therapeutic potential of Hsp70 activator against prion diseases using and models.
Front Cell Dev Biol
July 2024
Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Republic of Korea.
Introduction: Prion diseases are deadly neurodegenerative disorders in both animals and humans, causing the destruction of neural tissue and inducing behavioral manifestations. Heat shock proteins (Hsps), act as molecular chaperones by supporting the appropriate folding of proteins and eliminating the misfolded proteins as well as playing a vital role in cell signaling transduction, cell cycle, and apoptosis control. SW02 is a potent activator of Hsp 70 kDa (Hsp70).
View Article and Find Full Text PDFPHB2 Alleviates Neurotoxicity of Prion Peptide PrP via PINK1/Parkin-Dependent Mitophagy.
Int J Mol Sci
November 2023
Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
Prion diseases are a group of neurodegenerative diseases characterized by mitochondrial dysfunction and neuronal death. Mitophagy is a selective form of macroautophagy that clears injured mitochondria. Prohibitin 2 (PHB2) has been identified as a novel inner membrane mitophagy receptor that mediates mitophagy.
View Article and Find Full Text PDFCardiolipin externalization mediates prion protein (PrP) peptide 106-126-associated mitophagy and mitochondrial dysfunction.
Front Mol Neurosci
June 2023
National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, State Key Laboratories for Agrobiotechnology, Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, China.
Proper mitochondrial performance is imperative for the maintenance of normal neuronal function to prevent the development of neurodegenerative diseases. Persistent accumulation of damaged mitochondria plays a role in prion disease pathogenesis, which involves a chain of events that culminate in the generation of reactive oxygen species and neuronal death. Our previous studies have demonstrated that PINK1/Parkin-mediated mitophagy induced by PrP is defective and leads to an accumulation of damaged mitochondria after PrP treatment.
View Article and Find Full Text PDFRAB7A GTPase Is Involved in Mitophagosome Formation and Autophagosome-Lysosome Fusion in N2a Cells Treated with the Prion Protein Fragment 106-126.
Mol Neurobiol
March 2023
National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Failed communication between mitochondria and lysosomes causes dysfunctional mitochondria, which may induce mitochondria-related neurodegenerative diseases. Here, we show that RAB7A, a small GTPase of the Rab family, mediates the crosstalk between these two important organelles to maintain homeostasis in N2a cells treated with PrP. Specifically, we demonstrate that mitophagy deficiency in N2a cells caused by PrP is associated with dysregulated RAB7A localization in mitochondria.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!