PMID- 34719643
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20220210
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 44
IP  - 11
DP  - 2021
TI  - Neuroprotection by B355252 against Glutamate-Induced Cytotoxicity in Murine 
      Hippocampal HT-22 Cells Is Associated with Activation of ERK3 Signaling Pathway.
PG  - 1662-1669
LID - 10.1248/bpb.b21-00158 [doi]
AB  - Glutamate differentially affects the levels extracellular signal-regulated kinase 
      (ERK)1/2 and ERK3 and the protective effect of B355252, an aryl thiophene 
      compound, 
      4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-(piperazin-1-yl)phenoxy)thiophene-2-sulfonamide, 
      is associated with suppression of ERK1/2. The objectives of this study were to 
      further investigate the impact of B355252 on ERK3 and its downstream signaling 
      pathways affected by glutamate exposure in the mouse hippocampal HT-22 neuronal 
      cells. Murine hippocampal HT22 cells were incubated with glutamate and treated 
      with B355252. Cell viability was assessed, protein levels of pERK3, ERK3, 
      mitogen-activated protein kinase-activated protein kinase-5 (MAPKAPK-5), steroid 
      receptor coactivator 3 (SRC-3), p-S6 and S6 were measured using Western blotting, 
      and immunoreactivity of p-S6 was determined by immunocytochemistry. The results 
      reveal that glutamate markedly diminished the protein levels of p-ERK3 and its 
      downstream targets MK-5 and SRC-3 and increased p-S6, an indicator for 
      mechanistic target of rapamycin (mTOR) activation. Conversely, treatment with 
      B355252 protected the cells from glutamate-induced damage and prevented the 
      glutamate-caused declines of p-ERK3, MK-5 and SRC-3 and increase of p-S6. Our 
      study demonstrates that one of the mechanisms that glutamate mediates its 
      cytotoxicity is through suppression of ERK3 and that B355252 rescues the cells 
      from glutamate toxicity by reverting ERK3 level.
FAU - Ma, Yanni
AU  - Ma Y
AD  - Institute of Clinical Pharmacology, Department of Pharmacy, General Hospital of 
      Ningxia Medical University.
AD  - Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and 
      Technological Enterprise (BRITE), College of Health and Sciences, North Carolina 
      Central University.
FAU - Qi, Qi
AU  - Qi Q
AD  - Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and 
      Technological Enterprise (BRITE), College of Health and Sciences, North Carolina 
      Central University.
AD  - The Julis Chambers Biomedical Biotechnology Research Institute (BBRI), North 
      Carolina Central University.
FAU - He, Qingping
AU  - He Q
AD  - Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and 
      Technological Enterprise (BRITE), College of Health and Sciences, North Carolina 
      Central University.
FAU - Gilyazova, Nailya S
AU  - Gilyazova NS
AD  - Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and 
      Technological Enterprise (BRITE), College of Health and Sciences, North Carolina 
      Central University.
FAU - Ibeanu, Gordon
AU  - Ibeanu G
AD  - Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and 
      Technological Enterprise (BRITE), College of Health and Sciences, North Carolina 
      Central University.
FAU - Li, P Andy
AU  - Li PA
AD  - Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and 
      Technological Enterprise (BRITE), College of Health and Sciences, North Carolina 
      Central University.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (B355252)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Thiophenes)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 6)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Fluorescent Antibody Technique
MH  - Glutamic Acid/*toxicity
MH  - Hippocampus/*drug effects
MH  - MAP Kinase Signaling System/*drug effects
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 6/*metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Thiophenes/*pharmacology
OTO - NOTNLM
OT  - B355252
OT  - MK-5
OT  - cytotoxicity
OT  - extracellular signal-regulated kinase (ERK)3
OT  - glutamate
OT  - mechanistic target of rapamycin (mTOR)
EDAT- 2021/11/02 06:00
MHDA- 2022/02/11 06:00
CRDT- 2021/11/01 06:00
PHST- 2021/11/01 06:00 [entrez]
PHST- 2021/11/02 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
AID - 10.1248/bpb.b21-00158 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2021;44(11):1662-1669. doi: 10.1248/bpb.b21-00158.