PMID- 25027559
OWN - NLM
STAT- MEDLINE
DCOM- 20150911
LR  - 20211021
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 55
IP  - 2
DP  - 2015 Feb
TI  - KHSRP participates in manganese-induced neurotoxicity in rat striatum and PC12 
      cells.
PG  - 454-65
LID - 10.1007/s12031-014-0367-7 [doi]
AB  - Manganese (Mn) is an essential micronutrient. However, exposure to high doses of 
      Mn may lead to a neurological disease known as manganism, which is characterized 
      by marked brain neuronal loss. K-homology splicing regulator protein (KHSRP) is a 
      multifunctional RNA-binding protein and has been implicated in the regulation of 
      multiple cellular signaling associated with neuronal apoptosis and survival, such 
      as p38 mitogen-activated protein kinase (MAPK), nuclear factor kappaB (NF-kappaB), 
      and Wnt/beta-catenin pathways. In the present study, the role of KHSRP in Mn-induced 
      neurotoxicity was investigated in vivo using a rat model of chronic Mn exposure 
      and in vitro using differentiated PC12 cell cultures. Western blot and 
      immunohistochemical analyses showed a significant upregulation of KHSRP in rat 
      striatum following Mn exposure. Immunofluorescent labeling indicated that KHSRP 
      was localized mainly in neurons. Terminal deoxynucleotidyl transferase-mediated 
      biotinylated-dUTP nick end labeling (TUNEL) assay showed that KHSRP was mainly 
      distributed in apoptotic neurons. Increased KHSRP expression was positively 
      correlated with the upregulation of several apoptosis-related proteins, such as 
      p53, bax, and active caspase-3. In addition, significant co-localization of KHSRP 
      and active caspase-3 in neurons after Mn exposure was also observed, suggesting a 
      potential involvement of KHSRP in the regulation of Mn-induced striatal neuronal 
      apoptosis. Importantly, interference with KHSRP apparently decreased the level of 
      p53 and attenuated Mn-induced neuronal apoptosis. Taken together, these results 
      indicate that upregulation of KHSRP may be involved in the pathological process 
      underlying Mn neurotoxicity via the modulation of p53 signaling.
FAU - Shi, Shangshi
AU  - Shi S
AD  - Department of Occupational Medicine and Environmental Toxicology, School of 
      Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic 
      of China.
FAU - Zhao, Jianya
AU  - Zhao J
FAU - Yang, Lingling
AU  - Yang L
FAU - Nie, Xiaoke
AU  - Nie X
FAU - Han, Jingling
AU  - Han J
FAU - Ma, Xia
AU  - Ma X
FAU - Wan, Chunhua
AU  - Wan C
FAU - Jiang, Junkang
AU  - Jiang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140716
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (KHSRP protein, rat)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 42Z2K6ZL8P (Manganese)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Corpus Striatum/drug effects/*metabolism
MH  - Male
MH  - Manganese/*toxicity
MH  - Neurons/drug effects/metabolism
MH  - PC12 Cells
MH  - RNA-Binding Proteins/genetics/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Trans-Activators/genetics/*metabolism
MH  - Tumor Suppressor Protein p53/metabolism
EDAT- 2014/07/17 06:00
MHDA- 2015/09/12 06:00
CRDT- 2014/07/17 06:00
PHST- 2014/03/29 00:00 [received]
PHST- 2014/06/26 00:00 [accepted]
PHST- 2014/07/17 06:00 [entrez]
PHST- 2014/07/17 06:00 [pubmed]
PHST- 2015/09/12 06:00 [medline]
AID - 10.1007/s12031-014-0367-7 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2015 Feb;55(2):454-65. doi: 10.1007/s12031-014-0367-7. Epub 2014 
      Jul 16.