The cellular prion protein (PrPC) prevents apoptotic neuronal cell death and mitochondrial dysfunction induced by serum deprivation

Boe Hyun Kim, Hyoung Gon Lee, Jin Kyu Choi, Jae Il Kim, Eun Kyoung Choi, Richard I. Carp, Yong Sun Kim

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Prion diseases are transmissible neurodegenerative disorders that are invariably fatal in humans and animals. Although the nature of the infectious agent and pathogenic mechanisms of prion diseases are not clear, it has been reported that prion diseases may be associated with aberrant metabolism of cellular prion protein (PrPC). In various reports, it has been postulated that PrPC may be involved in one or more of the following: neurotransmitter metabolism, cell adhesion, signal transduction, copper metabolism, antioxidant activity or programmed cell death. Despite suggestive results supporting each of these mechanisms, the physiological function(s) of PrPC is not known. To investigate whether PrPC can prevent apoptotic cell death in prion diseases, we established the cell lines stably expressing PrPC from PrP knockout (PrP-/-) neuronal cells and examined the role of PrPC under apoptosis and/or serum-deprived condition. We found that PrP-/- cells were vulnerable to apoptotic cell death and that this vulnerability was rescued by the expression of PrP C. The expression levels of apoptosis-related proteins including p53, Bax, caspase-3, poly(ADP-ribose) polymerase (PARP) and cytochrome c were significantly increased in PrP-/- cells. In addition, Ca2+ levels of mitochondria were increased, whereas mitochondrial membrane potentials were decreased in PrP-/- cells. These results strongly suggest that PrPC may play a central role as an effective anti-apoptotic protein through caspase-dependent apoptotic pathways in mitochondria, supporting the concept that disruption of PrPC and consequent reduction of anti-apoptotic capacity of PrPC may be one of the pathogenic mechanisms of prion diseases.

Original languageEnglish
Pages (from-to)40-50
Number of pages11
JournalMolecular Brain Research
Issue number1
StatePublished - 29 Apr 2004
Externally publishedYes


  • Apoptosis
  • Degenerative disease, other
  • Disorders of the nervous system
  • PrP knockout cells
  • Prion diseases


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