PMID- 31443122
OWN - NLM
STAT- MEDLINE
DCOM- 20200911
LR  - 20200911
IS  - 1932-8494 (Electronic)
IS  - 1932-8486 (Linking)
VI  - 302
IP  - 12
DP  - 2019 Dec
TI  - The E3 Ubiquitin Ligase MARCH8 Regulates TNF-alpha-Induced Apoptosis in Hippocampal 
      Neurons by Targeting Myosin Light Chain 2 for Degradation.
PG  - 2271-2278
LID - 10.1002/ar.24238 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an important inflammatory cytokine that plays 
      a key role in neuronal damage. Elevated expression of TNF-alpha is associated with 
      numerous neurodegenerative diseases including Alzheimer's Disease and Parkinson's 
      Disease. However, the specific mechanism of the signaling events that trigger 
      TNF-alpha-mediated neurotoxicity remain unknown. In this study, we report that 
      intracerebroventricular injection of TNF-alpha in rat hippocampal neurons 
      down-regulates MLC2 and up-regulates MARCH8, an essential light chain and 
      regulatory myosin light chain of NM Myosin II, respectively. MARCH8 
      overexpression attenuates the degradation of MLC2 by promoting its ubiquitination 
      and degradation. Inhibition of MARCH8 by siRNA blocks caspase-3 activation and 
      apoptosis signaling, suggesting that TNF-alpha-induced apoptosis of neurons is 
      partially dependent on the accumulation of MARCH8 and the ubiquitination of MLC2. 
      Taken together, our data not only clarify the function of MARCH8 in TNF-alpha-induced 
      neurotoxicity, but also demonstrates that TNF-alpha promotes the MARCH8-MLC2 mediated 
      apoptosis of hippocampal neurons. Anat Rec, 302:2271-2278, 2019. (c) 2019 American 
      Association for Anatomy.
CI  - (c) 2019 American Association for Anatomy.
FAU - Guo, Shanglin
AU  - Guo S
AD  - The Affiliated Hospital of Medical College, QingDao University, Qingdao, China.
FAU - Zhang, Yongqing
AU  - Zhang Y
AD  - Qilu Hospital of Shandong University (Qingdao), Qingdao, China.
FAU - Wei, Chaoping
AU  - Wei C
AD  - Qingdao Women and Children's Hospital, Qingdao, China.
FAU - Shi, Lu
AU  - Shi L
AD  - 401 Hospital of the People's Liberation Army, Qingdao, China.
FAU - Feng, Yugong
AU  - Feng Y
AUID- ORCID: 0000-0002-9855-5949
AD  - The Affiliated Hospital of Medical College, QingDao University, Qingdao, China.
LA  - eng
PT  - Journal Article
DEP - 20190930
PL  - United States
TA  - Anat Rec (Hoboken)
JT  - Anatomical record (Hoboken, N.J. : 2007)
JID - 101292775
RN  - 0 (Myosin Light Chains)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (myosin light chain 2)
RN  - EC 2.3.2.27 (March8 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.6.1.- (Cardiac Myosins)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cardiac Myosins/*metabolism
MH  - Hippocampus/drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myosin Light Chains/*metabolism
MH  - Neurons/drug effects/*metabolism
MH  - *Proteolysis
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Ubiquitin-Protein Ligases/genetics/*metabolism
MH  - Ubiquitination
OTO - NOTNLM
OT  - TNF-alpha
OT  - apoptosis
OT  - march8
EDAT- 2019/08/24 06:00
MHDA- 2020/09/12 06:00
CRDT- 2019/08/24 06:00
PHST- 2018/08/28 00:00 [received]
PHST- 2019/04/28 00:00 [revised]
PHST- 2019/05/20 00:00 [accepted]
PHST- 2019/08/24 06:00 [pubmed]
PHST- 2020/09/12 06:00 [medline]
PHST- 2019/08/24 06:00 [entrez]
AID - 10.1002/ar.24238 [doi]
PST - ppublish
SO  - Anat Rec (Hoboken). 2019 Dec;302(12):2271-2278. doi: 10.1002/ar.24238. Epub 2019 
      Sep 30.