PMID- 29998403
OWN - NLM
STAT- MEDLINE
DCOM- 20190726
LR  - 20200722
IS  - 1573-7365 (Electronic)
IS  - 0885-7490 (Linking)
VI  - 33
IP  - 5
DP  - 2018 Oct
TI  - Hepatic encephalopathy changes mitochondrial dynamics and autophagy in the 
      substantia nigra.
PG  - 1669-1678
LID - 10.1007/s11011-018-0275-6 [doi]
AB  - Hepatic encephalopathy (HE) has been reported in more than 40% of patients with 
      cirrhosis in clinical practice. HE changes mitochondrial dysfunction. 
      Mitochondrial dynamics and autophagy are important for maintaining and removing 
      damaged mitochondria. We used molecular biology and morphology methods to 
      evaluate changes in mitochondrial dynamics and autophagy of the substantia nigra 
      (SN) and prefrontal cortex (PFC) in HE. In this study, we observed that HE 
      increased mitochondrial dynamics and autophagy in the SN, which was not seen in 
      the PFC. HE stimulated dynamin-related protein 1 (DRP1) transformation from the 
      cytosolic to the mitochondria within SN cells, which increased mitochondrial 
      fission and the number of mitochondria. The fusion protein L-OPA1 (long isoforms 
      of OPA1) was increased in the SN of HE mice. HE also increased the levels of 
      autophagy proteins PINK1/PARKIN and P62/LC3-B in the SN, which can selectively 
      remove damaged mitochondria and cell, respectively. Additionally, we used 
      electron microscopy to directly observe changes in mitochondrial morphology in 
      the SN of HE mice and found the number of mitochondria was increased. However, 
      there were no significant changes in the fission, fusion or autophagy proteins in 
      PFC-purified mitochondrial proteins in HE mice. The number of mitochondria also 
      did not show alterations in the PFC of HE mice compared with that in a sham 
      group. These results illustrate that mitochondria can protect themselves by 
      changing the dynamics and autophagy in the SN of HE mice. Changes in the 
      mitochondrial dynamics and autophagy related to HE can help repair damaged 
      mitochondria and provide a further understanding of the mechanisms of hepatic 
      encephalopathy.
FAU - Bai, Yunhu
AU  - Bai Y
AD  - Department of Hepatobiliary Surgery, Xi-Jing Hospital, Fourth Military Medical 
      University, Xi'an, 710032, China.
FAU - Wang, Yayun
AU  - Wang Y
AD  - Department of Anatomy and K.K. Leung Brain Research Centre, Fourth Military 
      Medical University, Xi'an, 710032, China.
FAU - Yang, Yanling
AU  - Yang Y
AD  - Department of Hepatobiliary Surgery, Xi-Jing Hospital, Fourth Military Medical 
      University, Xi'an, 710032, China. yangyanl@fmmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180711
PL  - United States
TA  - Metab Brain Dis
JT  - Metabolic brain disease
JID - 8610370
RN  - 0 (Carcinogens)
RN  - 075T165X8M (Thioacetamide)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (parkin protein)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (PTEN-induced putative kinase)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (Opa1 protein, mouse)
RN  - EC 3.6.5.5 (Dnm1l protein, mouse)
RN  - EC 3.6.5.5 (Dynamins)
MH  - Animals
MH  - *Autophagy
MH  - Behavior, Animal
MH  - Carcinogens/pharmacology
MH  - Cytosol/metabolism
MH  - Disease Models, Animal
MH  - Dynamins/metabolism
MH  - GTP Phosphohydrolases/metabolism
MH  - Hepatic Encephalopathy/*pathology
MH  - Liver Failure, Acute/chemically induced/complications
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/metabolism/pathology
MH  - *Mitochondrial Dynamics
MH  - Mitophagy
MH  - Prefrontal Cortex/metabolism
MH  - Protein Kinases/metabolism
MH  - Substantia Nigra/*pathology
MH  - Thioacetamide/pharmacology
MH  - Ubiquitin-Protein Ligases/metabolism
OTO - NOTNLM
OT  - Autophagy
OT  - Dynamics
OT  - Hepatic encephalopathy
OT  - Mitochondria
OT  - Prefrontal cortex
OT  - Substantia nigra
EDAT- 2018/07/13 06:00
MHDA- 2019/07/28 06:00
CRDT- 2018/07/13 06:00
PHST- 2018/01/25 00:00 [received]
PHST- 2018/06/19 00:00 [accepted]
PHST- 2018/07/13 06:00 [pubmed]
PHST- 2019/07/28 06:00 [medline]
PHST- 2018/07/13 06:00 [entrez]
AID - 10.1007/s11011-018-0275-6 [pii]
AID - 10.1007/s11011-018-0275-6 [doi]
PST - ppublish
SO  - Metab Brain Dis. 2018 Oct;33(5):1669-1678. doi: 10.1007/s11011-018-0275-6. Epub 
      2018 Jul 11.