Human prion protein-induced autophagy flux governs neuron cell damage in primary neuron cells.
An unusual molecular structure of the prion protein, PrPsc is found only in mammals with transmissible prion diseases. Prion protein stands for either the infectious pathogen itself or a main component of it. Recent studies suggest that autophagy is one of the major functions that keep cells alive and has a protective effect against the neurodegeneration. In this study, we investigated that the effect of human prion protein on autophagy-lysosomal system of primary neuronal cells. The treatment of human prion protein induced primary neuron cell death and decreased both LC3-II and p62 protein amount indicating autophagy flux activation. Electron microscope pictures confirmed the autophagic flux activation in neuron cells treated with prion protein. Inhibition of autophagy flux using pharmacological and genetic tools prevented neuron cell death induced by human prion protein. Autophagy flux induced by prion protein is more activated in prpc expressing cells than in prpc silencing cells. These data demonstrated that prion protein-induced autophagy flux is involved in neuron cell death in prion disease and suggest that autophagy flux might play a critical role in neurodegenerative diseases including prion disease.
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
Ji-Hong
JH
Moon
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
Ju-Hee
JH
Lee
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
Uddin Md
UM
Nazim
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
You-Jin
YJ
Lee
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
Jae-Won
JW
Seol
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
Seong-Kug
SK
Eo
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
John-Hwa
JH
Lee
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk, South Korea.
Sang-Youel
SY
Park
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000502:physiology*; D061251:Primary Cell Culture; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000502:physiology*; D000071456:Sequestosome-1 Protein / Q000378:metabolism
C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D011328:Prions; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; C082632:prion protein (106-126)
ATG5; Gerotarget; PrPc; autophagy flux; neurodegeneration; prion protein