PMID- 37874694
OWN - NLM
STAT- MEDLINE
DCOM- 20240205
LR  - 20240211
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 70
IP  - 2
DP  - 2024 Feb
TI  - P300/CBP Regulates HIF-1-Dependent Sympathetic Activation and Hypertension by 
      Intermittent Hypoxia.
PG  - 110-118
LID - 10.1165/rcmb.2022-0481OC [doi]
AB  - Obstructive sleep apnea (OSA), a widespread breathing disorder, leads to 
      intermittent hypoxia (IH). Patients with OSA and IH-treated rodents exhibit 
      heightened sympathetic nerve activity and hypertension. Previous studies reported 
      transcriptional activation of nicotinamide adenine dinucleotide phosphate (NADPH) 
      oxidases (Nox) by HIF-1 (hypoxia-inducible factor-1) contribute to autonomic 
      dysfunction in IH-treated rodents. Lysine acetylation, regulated by KATs (lysine 
      acetyltransferases) and KDACs (lysine deacetylases), activates gene transcription 
      and plays an important role in several physiological and pathological processes. 
      This study tested the hypothesis that acetylation of HIF-1alpha by p300/CBP 
      (CREB-binding protein) (KAT) activates Nox transcription, leading to sympathetic 
      activation and hypertension. Experiments were performed on 
      pheochromocytoma-12 cells and rats treated with IH. IH increased KAT activity, 
      p300/CBP protein, HIF-1alpha lysine acetylation, HIF-1 transcription, and HIF-1 
      binding to the Nox4 gene promoter in pheochromocytoma-12 cells, and these 
      responses were blocked by CTK7A, a selective p300/CBP inhibitor. Plasma 
      norepinephrine (index of sympathetic activation) and blood pressures were 
      elevated in IH-treated rats. These responses were associated with elevated 
      p300/CBP protein, HIF-1alpha stabilization, transcriptional activation of Nox2 and 
      Nox4 genes, and reactive oxygen species, and all these responses were absent in 
      CTK7A-treated IH rats. These findings suggest lysine acetylation of HIF-1alpha by 
      p300/CBP is an important contributor to sympathetic excitation and hypertension 
      by IH.
FAU - Wang, Ning
AU  - Wang N
AD  - Institute for Integrative Physiology and Center for Systems Biology of O2 
      Sensing, The University of Chicago, Chicago, Illinois.
FAU - Su, Xiaoyu
AU  - Su X
AD  - Institute for Integrative Physiology and Center for Systems Biology of O2 
      Sensing, The University of Chicago, Chicago, Illinois.
FAU - Sams, David
AU  - Sams D
AD  - Institute for Integrative Physiology and Center for Systems Biology of O2 
      Sensing, The University of Chicago, Chicago, Illinois.
FAU - Prabhakar, Nanduri R
AU  - Prabhakar NR
AD  - Institute for Integrative Physiology and Center for Systems Biology of O2 
      Sensing, The University of Chicago, Chicago, Illinois.
FAU - Nanduri, Jayasri
AU  - Nanduri J
AUID- ORCID: 0000-0003-3984-7447
AD  - Institute for Integrative Physiology and Center for Systems Biology of O2 
      Sensing, The University of Chicago, Chicago, Illinois.
LA  - eng
GR  - P01 HL144454/HL/NHLBI NIH HHS/United States
GR  - P01-HL144454/NH/NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - K3Z4F929H6 (Lysine)
RN  - EC 2.3.1.48 (p300-CBP Transcription Factors)
RN  - 0 (Hif1a protein, rat)
SB  - IM
CIN - Am J Respir Cell Mol Biol. 2024 Feb;70(2):87-88. PMID: 38109691
MH  - Animals
MH  - Rats
MH  - *Adrenal Gland Neoplasms
MH  - *Hypertension
MH  - Hypoxia/metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Lysine
MH  - p300-CBP Transcription Factors/genetics/metabolism
MH  - *Pheochromocytoma
MH  - *Sleep Apnea, Obstructive/complications
PMC - PMC10848695
OTO - NOTNLM
OT  - histone acetylases
OT  - hypoxia inducible factor-1
OT  - intermittent hypoxia
OT  - obstructive sleep apnea
OT  - p300/CBP
EDAT- 2023/10/24 18:42
MHDA- 2024/02/02 06:43
PMCR- 2024/10/24
CRDT- 2023/10/24 12:39
PHST- 2024/10/24 00:00 [pmc-release]
PHST- 2024/02/02 06:43 [medline]
PHST- 2023/10/24 18:42 [pubmed]
PHST- 2023/10/24 12:39 [entrez]
AID - 10.1165/rcmb.2022-0481OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2024 Feb;70(2):110-118. doi: 10.1165/rcmb.2022-0481OC.