PMID- 27722792
OWN - NLM
STAT- MEDLINE
DCOM- 20180131
LR  - 20181113
IS  - 1573-7365 (Electronic)
IS  - 0885-7490 (Print)
IS  - 0885-7490 (Linking)
VI  - 32
IP  - 1
DP  - 2017 Feb
TI  - Decreased sensitivity of palmitoyl protein thioesterase 1-deficient neurons to 
      chemical anoxia.
PG  - 275-279
LID - 10.1007/s11011-016-9919-6 [doi]
AB  - Infantile CLN1 disease, also known as infantile neuronal ceroid lipofuscinosis, 
      is a fatal childhood neurodegenerative disorder caused by mutations in the CLN1 
      gene. CLN1 encodes a soluble lysosomal enzyme, palmitoyl protein thioesterase 1 
      (PPT1), and it is still unclear why neurons are selectively vulnerable to the 
      loss of PPT1 enzyme activity in infantile CLN1 disease. To examine the effects of 
      PPT1 deficiency on several well-defined neuronal signaling and cell death 
      pathways, different toxic insults were applied in cerebellar granule neuron 
      cultures prepared from wild type (WT) and palmitoyl protein thioesterase 
      1-deficient (Ppt1 (-/-) ) mice, a model of infantile CLN1 disease. Glutamate 
      uptake inhibition by t-PDC (L-trans-pyrrolidine-2,4-dicarboxylic acid) or 
      Zn(2+)-induced general mitochondrial dysfunction caused similar toxicity in WT 
      and Ppt1 (-/-) cultures. Ppt1 (-/-) neurons, however, were more sensitive to 
      mitochondrial complex I inhibition by MPP(+) (1-methyl-4-phenylpyridinium), and 
      had significantly decreased sensitivity to chemical anoxia induced by the 
      mitochondrial complex IV inhibitor, sodium azide. Our results indicate that PPT1 
      deficiency causes alterations in the mitochondrial respiratory chain.
FAU - Meyer, Meredith
AU  - Meyer M
AD  - Sanford Children's Health Research Center, Sanford Research, 2301 E. 60th Street, 
      Sioux Falls, SD, 57104, USA.
FAU - Kovacs, Attila D
AU  - Kovacs AD
AD  - Sanford Children's Health Research Center, Sanford Research, 2301 E. 60th Street, 
      Sioux Falls, SD, 57104, USA.
AD  - Department of Pediatrics, Sanford School of Medicine, University of South Dakota 
      Sioux Falls, Sioux Falls, SD, 57104, USA.
FAU - Pearce, David A
AU  - Pearce DA
AD  - Sanford Children's Health Research Center, Sanford Research, 2301 E. 60th Street, 
      Sioux Falls, SD, 57104, USA. PearceD@SanfordHealth.org.
AD  - Department of Pediatrics, Sanford School of Medicine, University of South Dakota 
      Sioux Falls, Sioux Falls, SD, 57104, USA. PearceD@SanfordHealth.org.
LA  - eng
GR  - R01 NS044310/NS/NINDS NIH HHS/United States
GR  - R21 NS067147/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20161008
PL  - United States
TA  - Metab Brain Dis
JT  - Metabolic brain disease
JID - 8610370
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
RN  - R865A5OY8J (1-Methyl-4-phenylpyridinium)
SB  - IM
MH  - 1-Methyl-4-phenylpyridinium/pharmacology
MH  - Animals
MH  - Cell Hypoxia/*physiology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Mice
MH  - Mice, Knockout
MH  - Mutation
MH  - Neurons/cytology/drug effects/*metabolism
MH  - Thiolester Hydrolases/genetics/*metabolism
PMC - PMC5335868
MID - NIHMS851618
OTO - NOTNLM
OT  - Batten disease
OT  - Cerebellar granule neurons
OT  - Cytochrome c oxidase
OT  - Infantile CLN1 disease
OT  - Palmitoyl protein thioesterase 1
OT  - Ppt1 -/-
EDAT- 2016/10/11 06:00
MHDA- 2018/02/01 06:00
PMCR- 2018/02/01
CRDT- 2016/10/11 06:00
PHST- 2016/06/29 00:00 [received]
PHST- 2016/10/03 00:00 [accepted]
PHST- 2016/10/11 06:00 [pubmed]
PHST- 2018/02/01 06:00 [medline]
PHST- 2016/10/11 06:00 [entrez]
PHST- 2018/02/01 00:00 [pmc-release]
AID - 10.1007/s11011-016-9919-6 [pii]
AID - 10.1007/s11011-016-9919-6 [doi]
PST - ppublish
SO  - Metab Brain Dis. 2017 Feb;32(1):275-279. doi: 10.1007/s11011-016-9919-6. Epub 
      2016 Oct 8.