PMID- 33437989
OWN - NLM
STAT- MEDLINE
DCOM- 20211004
LR  - 20220201
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 30
IP  - 1
DP  - 2021 Mar 25
TI  - Glutathione S-transferase Pi (Gstp) proteins regulate neuritogenesis in the 
      developing cerebral cortex.
PG  - 30-45
LID - 10.1093/hmg/ddab003 [doi]
AB  - GSTP proteins are metabolic enzymes involved in the removal of oxidative stress 
      and intracellular signaling and also have inhibitory effects on JNK activity. 
      However, the functions of Gstp proteins in the developing brain are unknown. In 
      mice, there are three Gstp proteins, Gstp1, 2 and 3, whereas there is only one 
      GSTP in humans. By reverse transcription-polymerase chain reaction (RT-PCR) 
      analysis, we found that Gstp1 was expressed beginning at E15.5 in the cortex, but 
      Gstp2 and 3 started expressing at E18.5. Gstp 1 and 2 knockdown (KD) caused 
      decreased neurite number in cortical neurons, implicating them in neurite 
      initiation. Using in utero electroporation (IUE) to knock down Gstp1 and 2 in 
      layer 2/3 pyramidal neurons in vivo, we found abnormal swelling of the apical 
      dendrite at P3 and reduced neurite number at P15. Using time-lapse live imaging, 
      we found that the apical dendrite orientation was skewed compared with the 
      control. We explored the molecular mechanism and found that JNK inhibition 
      rescued reduced neurite number caused by Gstp knockdown, indicating that Gstp 
      regulates neurite formation through JNK signaling. Thus, we found novel functions 
      of Gstp proteins in neurite initiation during cortical development. These 
      findings not only provide novel functions of Gstp proteins in neuritogenesis 
      during cortical development but also help us to understand the complexity of 
      neurite formation.
CI  - (c) The Author(s) 2021. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Liu, Xiaonan
AU  - Liu X
AD  - Department of Pharmacology and Physiology, Drexel University College of Medicine, 
      Philadelphia, PA 19129 USA.
FAU - Blazejewski, Sara M
AU  - Blazejewski SM
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 
      Philadelphia, PA 19129 USA.
FAU - Bennison, Sarah A
AU  - Bennison SA
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 
      Philadelphia, PA 19129 USA.
FAU - Toyo-Oka, Kazuhito
AU  - Toyo-Oka K
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 
      Philadelphia, PA 19129 USA.
LA  - eng
GR  - F31 HD103405/HD/NICHD NIH HHS/United States
GR  - F31 NS113404/NS/NINDS NIH HHS/United States
GR  - R01 NS096098/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Gstp2 protein, mouse)
RN  - EC 2.5.1.18 (Glutathione S-Transferase pi)
RN  - EC 2.5.1.18 (Gstp1 protein, mouse)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Cerebral Cortex/growth & development/*metabolism
MH  - Dendrites/genetics/pathology
MH  - Embryonic Development/genetics
MH  - Gene Expression Regulation, Developmental/genetics
MH  - Glutathione/genetics
MH  - Glutathione S-Transferase pi/*genetics
MH  - Humans
MH  - MAP Kinase Signaling System/genetics
MH  - Mice
MH  - Neurites/metabolism/pathology
MH  - Neurogenesis/*genetics
MH  - Oxidative Stress/genetics
MH  - Pyramidal Cells/metabolism/pathology
PMC - PMC8033146
EDAT- 2021/01/14 06:00
MHDA- 2021/10/05 06:00
PMCR- 2022/01/12
CRDT- 2021/01/13 06:14
PHST- 2020/08/28 00:00 [received]
PHST- 2020/12/21 00:00 [revised]
PHST- 2021/01/04 00:00 [accepted]
PHST- 2021/01/14 06:00 [pubmed]
PHST- 2021/10/05 06:00 [medline]
PHST- 2021/01/13 06:14 [entrez]
PHST- 2022/01/12 00:00 [pmc-release]
AID - 6089120 [pii]
AID - ddab003 [pii]
AID - 10.1093/hmg/ddab003 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2021 Mar 25;30(1):30-45. doi: 10.1093/hmg/ddab003.