PMID- 25231392
OWN - NLM
STAT- MEDLINE
DCOM- 20150617
LR  - 20211021
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 34
IP  - 5
DP  - 2014 Nov
TI  - Gingerol prevents prion protein-mediated neuronal toxicity by regulating HIF 
      prolyl hydroxylase 2 and prion protein.
PG  - 1268-76
LID - 10.3892/ijmm.2014.1936 [doi]
AB  - Prion diseases are a family of progressive neurodegenerative disorders, which are 
      fatal in the majority of cases and affect both humans and domestic animals. Prion 
      protein (PrP) (106-126) retains the neurotoxic properties of the entire 
      pathological PrPsc and it is generally used as a reasonable model to study the 
      mechanisms responsible for prion diseases. In our previous studies, we 
      demonstrated that hypoxia-inducible factor (HIF)-1alpha is involved in the 
      gingerol-mediated protection of neuronal cells. HIF mediates cellular adaptations 
      to low oxygen. Prolyl hydroxylase domain-containing protein 2 (PHD2) is an oxygen 
      sensor that hydroxylates the HIF-alpha-subunit, promoting its proteasomal degradation 
      under normoxic conditions. Thus, in the present study we wished to determine 
      whether gingerol inhibits the catalytic activity of PHD2 and prevents HIF-1alpha 
      protein proteasomal degradation, thereby preventing the occurrence of 
      PrP (106-126)-induced neuronal apoptosis. We used the pharmacological inhibition 
      of PHD2 by dimethyloxalylglycine (DMOG) or deferoxamine (DFO) and the genetic 
      inhibition of HIF-1alpha by HIF-1alpha small interfering RNA (siRNA) to block the effects 
      of gingerol against PrP (106-126)-induced neurotoxicity. Our results demonstrated 
      that gingerol prevented PrP (106‑126)-induced neuronal apoptosis by upregulating 
      HIF-1alpha and inhibiting the catalytic activity of PHD2 under normoxic conditions. 
      Moreover, the protective effects of gingerol against PrP (106-126)-induced 
      neuronal apoptosis were associated with the upregulation of the expression of 
      cellular prion protein (PrPc). In conclusion, our results indicate that gingerol 
      has therapeutic potential for use in the treatment or prevention of prion 
      diseases, and its inhibitory effects on the catalytic activity of PHD2 may be of 
      clinical benefit.
FAU - Park, Yang-Gyu
AU  - Park YG
AD  - Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National 
      University, Jeonju, Jeonbuk 561-756, Republic of Korea.
FAU - Park, Sang-Youel
AU  - Park SY
AD  - Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National 
      University, Jeonju, Jeonbuk 561-756, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140916
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Catechols)
RN  - 0 (Fatty Alcohols)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Peptide Fragments)
RN  - 0 (Prions)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (prion protein (106-126))
RN  - 925QK2Z900 (gingerol)
RN  - EC 1.14.11.2 (EGLN1 protein, human)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Catechols/*pharmacology
MH  - Cell Line, Tumor
MH  - Fatty Alcohols/*pharmacology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases/genetics/*metabolism
MH  - Oxygen
MH  - Peptide Fragments/genetics/metabolism
MH  - Prion Diseases/*drug therapy/*genetics/prevention & control
MH  - Prions/genetics/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Up-Regulation
PMC - PMC4199419
EDAT- 2014/09/19 06:00
MHDA- 2015/06/18 06:00
PMCR- 2014/09/16
CRDT- 2014/09/19 06:00
PHST- 2014/03/05 00:00 [received]
PHST- 2014/09/12 00:00 [accepted]
PHST- 2014/09/19 06:00 [entrez]
PHST- 2014/09/19 06:00 [pubmed]
PHST- 2015/06/18 06:00 [medline]
PHST- 2014/09/16 00:00 [pmc-release]
AID - ijmm-34-05-1268 [pii]
AID - 10.3892/ijmm.2014.1936 [doi]
PST - ppublish
SO  - Int J Mol Med. 2014 Nov;34(5):1268-76. doi: 10.3892/ijmm.2014.1936. Epub 2014 Sep 
      16.