PMID- 31409917
OWN - NLM
STAT- MEDLINE
DCOM- 20201104
LR  - 20230607
IS  - 1348-4214 (Electronic)
IS  - 0916-9636 (Linking)
VI  - 42
IP  - 12
DP  - 2019 Dec
TI  - Augmented O-GlcNAcylation attenuates intermittent hypoxia-induced cardiac 
      remodeling through the suppression of NFAT and NF-kappaB activities in mice.
PG  - 1858-1871
LID - 10.1038/s41440-019-0311-x [doi]
AB  - Type 2 diabetes mellitus (T(2)DM) has been reported to be associated with cardiac 
      remodeling. Although O-GlcNAcylation is known to be elevated in diabetic and 
      ischemic hearts, the effects of O-GlcNAcylation on cardiac remodeling induced by 
      intermittent hypoxia (IH), such as sleep apnea syndrome (SAS), remain unknown. To 
      evaluate the effects, we induced IH in wild-type (WT) and transgenic O-GlcNAc 
      transferase (Ogt-Tg) mice. Two weeks of IH increased O-GlcNAcylation in the heart 
      tissues of both strains of mice, whereas O-GlcNAcylation in Ogt-Tg mice was 
      significantly higher than that in WT mice under both normoxic and IH conditions. 
      WT mice exhibited cardiac remodeling after IH, whereas cardiac remodeling was 
      significantly attenuated in Ogt-Tg mice. Oxidative stress and apoptosis increased 
      after IH in both strains of mice, whereas the rate of increase in these processes 
      in Ogt-Tg mice was significantly lower than that in WT mice. To examine the 
      mechanism of cardiac remodeling attenuation in Ogt-Tg mice after IH, the effects 
      of O-GlcNAcylation on the activities of the master regulators nuclear factor of 
      activated T cells (NFAT) and NF-kappaB were determined. The O-GlcNAcylation of 
      GSK-3beta, a negative regulator of NFAT, was significantly increased in Ogt-Tg mice, 
      whereas the phosphorylation of GSK-3beta was reciprocally reduced. The same result 
      was observed for NF-kappaB p65. An in vitro reporter assay showed that the 
      augmentation of O-GlcNAcylation by an O-GlcNAcase inhibitor suppressed NFAT and 
      NF-kappaB promoter activity. These data suggest that augmented O-GlcNAcylation 
      mitigates IH-induced cardiac remodeling by suppressing NFAT and NF-kappaB activities 
      through the O-GlcNAcylation of GSK-3beta and NF-kappaB p65.
FAU - Nakagawa, Takatoshi
AU  - Nakagawa T
AD  - Department of Pharmacology, Osaka Medical College, Osaka, Japan.
FAU - Furukawa, Yuichi
AU  - Furukawa Y
AD  - Department of Pharmacology, Osaka Medical College, Osaka, Japan.
AD  - Department of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of 
      Pharmaceutical Sciences, Osaka, Japan.
FAU - Hayashi, Tetsuya
AU  - Hayashi T
AD  - Department of Pharmacology, Osaka Medical College, Osaka, Japan.
AD  - Department of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of 
      Pharmaceutical Sciences, Osaka, Japan.
FAU - Nomura, Atsuo
AU  - Nomura A
AD  - Department of Pharmacology, Osaka Medical College, Osaka, Japan.
AD  - Department of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of 
      Pharmaceutical Sciences, Osaka, Japan.
FAU - Yokoe, Shunichi
AU  - Yokoe S
AD  - Department of Pharmacology, Osaka Medical College, Osaka, Japan.
FAU - Moriwaki, Kazumasa
AU  - Moriwaki K
AD  - Department of Pharmacology, Osaka Medical College, Osaka, Japan.
FAU - Kato, Ryuji
AU  - Kato R
AD  - Department of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of 
      Pharmaceutical Sciences, Osaka, Japan.
FAU - Ijiri, Yoshio
AU  - Ijiri Y
AD  - Department of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of 
      Pharmaceutical Sciences, Osaka, Japan.
FAU - Yamaguchi, Takehiro
AU  - Yamaguchi T
AD  - Department of Cardiovascular Medicine, Osaka City University Graduate School of 
      Medicine, Osaka, Japan.
AD  - Department of Pharmacology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Izumi, Yasukatsu
AU  - Izumi Y
AD  - Department of Pharmacology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Yoshiyama, Minoru
AU  - Yoshiyama M
AD  - Department of Cardiovascular Medicine, Osaka City University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Asahi, Michio
AU  - Asahi M
AD  - Department of Pharmacology, Osaka Medical College, Osaka, Japan. 
      masahi@osaka-med.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190813
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (NF-kappa B)
RN  - 0 (NFATC Transcription Factors)
RN  - EC 2.4.1.- (N-Acetylglucosaminyltransferases)
RN  - EC 2.4.1.- (UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
SB  - IM
CIN - Hypertens Res. 2023 Jan 13;:. PMID: 36635529
MH  - Acylation
MH  - Animals
MH  - Cell Line
MH  - Diabetes Mellitus, Type 2/complications/pathology
MH  - Echocardiography
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Hypoxia/*pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Myocardium/metabolism/pathology
MH  - N-Acetylglucosaminyltransferases/genetics/*metabolism
MH  - NF-kappa B/*metabolism
MH  - NFATC Transcription Factors/*metabolism
MH  - Oxidative Stress
MH  - Phosphorylation
MH  - *Ventricular Remodeling
OTO - NOTNLM
OT  - GSK-3beta
OT  - NF-kappaB
OT  - NFAT
OT  - O-GlcNAcylation
OT  - cardiac remodeling
EDAT- 2019/08/15 06:00
MHDA- 2020/11/05 06:00
CRDT- 2019/08/15 06:00
PHST- 2019/03/01 00:00 [received]
PHST- 2019/07/03 00:00 [accepted]
PHST- 2019/06/04 00:00 [revised]
PHST- 2019/08/15 06:00 [pubmed]
PHST- 2020/11/05 06:00 [medline]
PHST- 2019/08/15 06:00 [entrez]
AID - 10.1038/s41440-019-0311-x [pii]
AID - 10.1038/s41440-019-0311-x [doi]
PST - ppublish
SO  - Hypertens Res. 2019 Dec;42(12):1858-1871. doi: 10.1038/s41440-019-0311-x. Epub 
      2019 Aug 13.