PMID- 35012414
OWN - NLM
STAT- MEDLINE
DCOM- 20230331
LR  - 20230331
IS  - 1029-2470 (Electronic)
IS  - 1029-2470 (Linking)
VI  - 55
IP  - 9-10
DP  - 2021 Oct
TI  - The downregulation of NADPH oxidase Nox4 during hypoxia in hemangioendothelioma 
      cells: a possible role of p22(phox) on Nox4 protein stability.
PG  - 996-1004
LID - 10.1080/10715762.2021.2009116 [doi]
AB  - NADPH oxidase (Nox) 4 produces H(2)O(2) by forming a heterodimer with p22(phox) 
      and is involved in hemangioendothelioma development through monocyte 
      chemoattractant protein-1 (MCP-1) upregulation. Here, we show that Nox4 protein 
      levels were maintained by p22(phox) in hemangioendothelioma cells and Nox4 
      protein stability was dependent on p22(phox) coexpression. Conversely, the 
      degradation of Nox4 monomer was enhanced by p22(phox) knockdown. Under hypoxic 
      conditions in hemangioendothelioma cells, p22(phox) was downregulated at the mRNA 
      and protein levels. Downregulation of p22(phox) protein resulted in the enhanced 
      degradation of Nox4 protein in hypoxia-treated hemangioendothelioma cells. In 
      contrast, Nox2, a Nox isoform, was not altered at the protein level under hypoxic 
      conditions. Nox2 exhibited a higher affinity for p22(phox) compared with Nox4, 
      suggesting that when coexpressed with Nox4 in the same cells, Nox2 acts as a 
      competitor. Nox2 knockdown restored Nox4 protein levels partially reduced by 
      hypoxic treatment. Thus, Nox4 protein levels were attenuated in hypoxia-treated 
      cells resulting from p22(phox) depletion. MCP-1 secretion was decreased 
      concurrently with hypoxia-induced Nox4 downregulation compared with that under 
      normoxia.
FAU - Miyano, Kei
AU  - Miyano K
AUID- ORCID: 0000-0002-3892-0393
AD  - Department of Biochemistry, Kawasaki Medical School, Okayama, Japan.
FAU - Okamoto, Shuichiro
AU  - Okamoto S
AUID- ORCID: 0000-0001-9274-1022
AD  - Department of Biochemistry, Kawasaki Medical School, Okayama, Japan.
FAU - Yamauchi, Akira
AU  - Yamauchi A
AUID- ORCID: 0000-0001-9205-6922
AD  - Department of Biochemistry, Kawasaki Medical School, Okayama, Japan.
FAU - Kawai, Chikage
AU  - Kawai C
AD  - Department of Biochemistry, Kawasaki Medical School, Okayama, Japan.
FAU - Kajikawa, Mizuho
AU  - Kajikawa M
AUID- ORCID: 0000-0002-8259-0870
AD  - Laboratory of Microbiology, Showa Pharmaceutical University, Machida, Japan.
FAU - Kiyohara, Takuya
AU  - Kiyohara T
AD  - Department of Cerebrovascular Disease and Neurology, Hakujyuji Hospital, Fukuoka, 
      Japan.
AD  - Department of Medicine and Clinical Science, Graduate School of Medical Sciences, 
      Kyushu University, Fukuoka, Japan.
FAU - Itsumi, Momoe
AU  - Itsumi M
AD  - Department of Oral Microbiology and Immunology, Showa University, Shinagawa, 
      Japan.
FAU - Taura, Masahiko
AU  - Taura M
AD  - Department of Otorhinolaryngology, Faculty of Medicine, Fukuoka University, 
      Fukuoka City, Japan.
FAU - Kuribayashi, Futoshi
AU  - Kuribayashi F
AD  - Department of Biochemistry, Kawasaki Medical School, Okayama, Japan.
LA  - eng
PT  - Journal Article
DEP - 20220111
PL  - England
TA  - Free Radic Res
JT  - Free radical research
JID - 9423872
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.- (NOX4 protein, human)
RN  - EC 1.6.3.- (Nox4 protein, mouse)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Down-Regulation
MH  - *Hemangioendothelioma
MH  - Hydrogen Peroxide/metabolism
MH  - Hypoxia/genetics
MH  - NADPH Oxidase 4/genetics/metabolism
MH  - *NADPH Oxidases/genetics/metabolism
MH  - Protein Stability
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - NADPH oxidase 4 (Nox4)
OT  - hemangioendothelioma
OT  - hypoxia
OT  - monocyte chemoattractant protein-1 (MCP-1)
OT  - p22phox
OT  - reactive oxygen species (ROS)
EDAT- 2022/01/12 06:00
MHDA- 2022/02/22 06:00
CRDT- 2022/01/11 05:46
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/02/22 06:00 [medline]
PHST- 2022/01/11 05:46 [entrez]
AID - 10.1080/10715762.2021.2009116 [doi]
PST - ppublish
SO  - Free Radic Res. 2021 Oct;55(9-10):996-1004. doi: 10.1080/10715762.2021.2009116. 
      Epub 2022 Jan 11.