PMID- 29171783
OWN - NLM
STAT- MEDLINE
DCOM- 20180813
LR  - 20181113
IS  - 2058-7384 (Electronic)
IS  - 0394-6320 (Print)
IS  - 0394-6320 (Linking)
VI  - 30
IP  - 4
DP  - 2017 Dec
TI  - Hyperhomocysteinemia-induced autophagy and apoptosis with downregulation of hairy 
      enhancer of split 1/5 in cortical neurons in mice.
PG  - 371-382
LID - 10.1177/0394632017740061 [doi]
AB  - It has been reported that hyperhomocysteinemia (HHcy) is associated with 
      neurodegenerative and cardiovascular diseases. However, little is known about 
      brain histomorphology, neuronal organelles, and hairy enhancer of split ( hes) 
      expression under HHcy. In this study, non-HHcy and HHcy induced by 
      high-methionine diet in apolipoprotein E-deficient (Apo E(-/-)) mice were 
      comparatively investigated. The histomorphology, ultrastructure, autophagosomes, 
      apoptosis, and expression of proteins, HES1, HES5 and P62, were designed to 
      assess the effects of HHcy on brain. The results showed that compared to the 
      non-HHcy mice, the HHcy group had an increase in autophagosomes, vacuolization in 
      mitochondria, and neuron apoptosis; treatment with folate and vitamin B(12) 
      reduced the extent of these lesions. However, the elementary histomorphology, the 
      numbers of cortical neurons, and Nissl bodies had no significant difference 
      between the HHcy and the non-HHcy groups or the group treated with folate and 
      vitamin B(12). Immunohistochemistry and immunofluorescence demonstrated a 
      decrease in HES1- or HES5-positive neurons in the HHcy group when compared to the 
      non-HHcy groups, wild-type, and Apo E(-/-) controls, or the HHcy mice with folate 
      and vitamin B(12) supplement. Western blots showed that HHcy induced a decreased 
      expression of HES1 and HES5, or P62, in which the expression of HES1 and P62 was 
      elevated by treating with folate and vitamin B(12) supplement. These results 
      suggest that HHcy-enhanced brain damage is associated with increased autophagy 
      and neuronal apoptosis in Apo E(-/-) mice, in which downregulation of hes1 and 
      hes5 is involved.
FAU - Zhang, Jing-Wen
AU  - Zhang JW
AD  - 1 Key Laboratory of Biomedical Information Engineering of Ministry of Education 
      and Institute of Immunopathology, Medical School, Xi'an Jiaotong University, 
      Xi'an, China.
AD  - 2 School of Basic Medical Science, Ningxia Key Laboratory of Cerebrocranial 
      Diseases-Incubation Base of National Key Laboratory, Ningxia Medical University, 
      Yinchuan, China.
FAU - Yan, Ru
AU  - Yan R
AD  - 2 School of Basic Medical Science, Ningxia Key Laboratory of Cerebrocranial 
      Diseases-Incubation Base of National Key Laboratory, Ningxia Medical University, 
      Yinchuan, China.
AD  - 3 Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, China.
FAU - Tang, Yu-Sheng
AU  - Tang YS
AD  - 2 School of Basic Medical Science, Ningxia Key Laboratory of Cerebrocranial 
      Diseases-Incubation Base of National Key Laboratory, Ningxia Medical University, 
      Yinchuan, China.
FAU - Guo, Yong-Zhen
AU  - Guo YZ
AD  - 2 School of Basic Medical Science, Ningxia Key Laboratory of Cerebrocranial 
      Diseases-Incubation Base of National Key Laboratory, Ningxia Medical University, 
      Yinchuan, China.
FAU - Chang, Yue
AU  - Chang Y
AD  - 2 School of Basic Medical Science, Ningxia Key Laboratory of Cerebrocranial 
      Diseases-Incubation Base of National Key Laboratory, Ningxia Medical University, 
      Yinchuan, China.
FAU - Jing, Li
AU  - Jing L
AD  - 2 School of Basic Medical Science, Ningxia Key Laboratory of Cerebrocranial 
      Diseases-Incubation Base of National Key Laboratory, Ningxia Medical University, 
      Yinchuan, China.
FAU - Wang, Yi-Li
AU  - Wang YL
AD  - 1 Key Laboratory of Biomedical Information Engineering of Ministry of Education 
      and Institute of Immunopathology, Medical School, Xi'an Jiaotong University, 
      Xi'an, China.
FAU - Zhang, Jian-Zhong
AU  - Zhang JZ
AD  - 2 School of Basic Medical Science, Ningxia Key Laboratory of Cerebrocranial 
      Diseases-Incubation Base of National Key Laboratory, Ningxia Medical University, 
      Yinchuan, China.
AD  - 4 Department of Pathology, Ningxia Medical University, Yinchuan, China.
LA  - eng
PT  - Journal Article
DEP - 20171124
PL  - England
TA  - Int J Immunopathol Pharmacol
JT  - International journal of immunopathology and pharmacology
JID - 8911335
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factor HES-1)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 148591-48-4 (HES5 protein, human)
RN  - 149348-15-2 (HES1 protein, human)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Autophagy
MH  - Basic Helix-Loop-Helix Transcription Factors/*metabolism
MH  - Down-Regulation
MH  - Frontal Lobe/metabolism/ultrastructure
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/blood/*metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout, ApoE
MH  - Microscopy, Electron, Transmission
MH  - Neurons/*metabolism/ultrastructure
MH  - Repressor Proteins/*metabolism
MH  - Transcription Factor HES-1/*metabolism
PMC - PMC5806807
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - hairy enhancer of split
OT  - homocysteine
OT  - neuron
COIS- Declaration of conflicting interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2017/11/25 06:00
MHDA- 2018/08/14 06:00
PMCR- 2017/12/01
CRDT- 2017/11/25 06:00
PHST- 2017/11/25 06:00 [pubmed]
PHST- 2018/08/14 06:00 [medline]
PHST- 2017/11/25 06:00 [entrez]
PHST- 2017/12/01 00:00 [pmc-release]
AID - 10.1177_0394632017740061 [pii]
AID - 10.1177/0394632017740061 [doi]
PST - ppublish
SO  - Int J Immunopathol Pharmacol. 2017 Dec;30(4):371-382. doi: 
      10.1177/0394632017740061. Epub 2017 Nov 24.