Cellular cholesterol enrichment prevents prion peptide-induced neuron cell damages.
The prion diseases are neurodegenerative disorders characterized by the conversion of the PrPc (normal cellular prion) to the PrPsc (misfolded isoform). The accumulation of PrPsc within the central nervous system (CNS) leads to neurocytotoxicity by increasing oxidative stress. In addition, many neurodegenerative disorders including prion, Parkinson's and Alzheimer's diseases may be regulated by cholesterol homeostasis. The effects of cholesterol balance on prion protein-mediated neurotoxicity and ROS (reactive oxygen species) generation were the focus of this study. Cholesterol treatment inhibited PrP (106-126)-induced neuronal cell death and ROS generation in SH-SY5Y neuroblastoma cells. In addition, the PrP (106-126)-mediated increase of p53, p-p38, p-ERK and the decrease of Bcl-2 were blocked by cholesterol treatment. These results indicated that cellular cholesterol enrichment is a key regulator of PrP-106-126-mediated oxidative stress and neurotoxicity. Taken together, the results of this study suggest that modulation of cellular cholesterol appears to prevent the neuronal cell death caused by prion peptides.
Jeong
Jae-Kyo
JK
Chonbuk National University, Center for Healthcare Technology Development, Bio-Safety Research Institute, College of Veterinary Medicine, Jeonju, Jeonbuk 561-756, South Korea.
Seol
Jae-Won
JW
Moon
Myung-Hee
MH
Seo
Jae-Suk
JS
Lee
You-Jin
YJ
Kim
Jin-Shang
JS
Park
Sang-Youel
SY
D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011328:Prions / Q000378:metabolism* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
D010446:Peptide Fragments; D011328:Prions; D017382:Reactive Oxygen Species; C082632:prion protein (106-126); D002784:Cholesterol