PMID- 36511516
OWN - NLM
STAT- MEDLINE
DCOM- 20230208
LR  - 20240202
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 324
IP  - 2
DP  - 2023 Feb 1
TI  - Mitoquinone mesylate attenuates pathological features of lean and obese allergic 
      asthma in mice.
PG  - L141-L153
LID - 10.1152/ajplung.00249.2022 [doi]
AB  - Obesity is associated with severe, difficult-to-control asthma, and increased 
      airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an 
      important source of oxidative stress in asthma, leading us to hypothesize that 
      targeting mROS in obese allergic asthma might be an effective treatment. Using a 
      mouse model of house dust mite (HDM)-induced allergic airway disease in mice fed 
      a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant 
      MitoQuinone (MitoQ), we investigated the effects of obesity and ROS on 
      HDM-induced airway inflammation, remodeling, and airway hyperresponsiveness 
      (AHR). Obese allergic mice showed increased lung tissue eotaxin, airway tissue 
      eosinophilia, and AHR compared with lean allergic mice. MitoQ reduced airway 
      inflammation, remodeling, and hyperreactivity in both lean and obese allergic 
      mice, and tissue eosinophilia in obese-allergic mice. Similar effects were 
      observed with decyl triphosphonium (dTPP(+)), the hydrophobic cationic moiety of 
      MitoQ lacking ubiquinone. HDM-induced oxidative sulfenylation of proteins was 
      increased particularly in HFD mice. Although only MitoQ reduced sulfenylation of 
      proteins involved in protein folding in the endoplasmic reticulum (ER), ER stress 
      was attenuated by both MitoQ and dTPP(+) suggesting the anti-allergic effects of 
      MitoQ are mediated in part by effects of its hydrophobic dTPP(+) moiety reducing 
      ER stress. In summary, oxidative signaling is an important mediator of allergic 
      airway disease. MitoQ, likely through reducing protein oxidation and affecting 
      the UPR pathway, might be effective for the treatment of asthma and specific 
      features of obese asthma.
FAU - Chandrasekaran, Ravishankar
AU  - Chandrasekaran R
AD  - Department of Medicine, University of Vermont, Burlington, Vermont.
FAU - Bruno, Sierra R
AU  - Bruno SR
AD  - Department of Pathology and Laboratory Medicine, University of Vermont, 
      Burlington, Vermont.
FAU - Mark, Zoe F
AU  - Mark ZF
AD  - Department of Pathology and Laboratory Medicine, University of Vermont, 
      Burlington, Vermont.
FAU - Walzer, Joseph
AU  - Walzer J
AD  - Department of Pathology and Laboratory Medicine, University of Vermont, 
      Burlington, Vermont.
FAU - Caffry, Sarah
AU  - Caffry S
AD  - Department of Medicine, University of Vermont, Burlington, Vermont.
FAU - Gold, Clarissa
AU  - Gold C
AD  - Department of Biology and Vermont Biomedical Research Network Proteomics 
      Facility, University of Vermont, Burlington, Vermont.
FAU - Kumar, Amit
AU  - Kumar A
AUID- ORCID: 0000-0002-7043-3798
AD  - Department of Pathology and Laboratory Medicine, University of Vermont, 
      Burlington, Vermont.
FAU - Chamberlain, Nicolas
AU  - Chamberlain N
AD  - Department of Pathology and Laboratory Medicine, University of Vermont, 
      Burlington, Vermont.
FAU - Butzirus, Isabella M
AU  - Butzirus IM
AD  - Department of Medicine, University of Vermont, Burlington, Vermont.
FAU - Morris, Carolyn R
AU  - Morris CR
AD  - Department of Medicine, University of Vermont, Burlington, Vermont.
FAU - Daphtary, Nirav
AU  - Daphtary N
AD  - Department of Medicine, University of Vermont, Burlington, Vermont.
FAU - Aliyeva, Minara
AU  - Aliyeva M
AD  - Department of Medicine, University of Vermont, Burlington, Vermont.
FAU - Lam, Ying-Wai
AU  - Lam YW
AD  - Department of Biology and Vermont Biomedical Research Network Proteomics 
      Facility, University of Vermont, Burlington, Vermont.
FAU - van der Vliet, Albert
AU  - van der Vliet A
AUID- ORCID: 0000-0003-0923-0016
AD  - Department of Pathology and Laboratory Medicine, University of Vermont, 
      Burlington, Vermont.
FAU - Janssen-Heininger, Yvonne
AU  - Janssen-Heininger Y
AUID- ORCID: 0000-0002-2735-8745
AD  - Department of Pathology and Laboratory Medicine, University of Vermont, 
      Burlington, Vermont.
FAU - Poynter, Matthew E
AU  - Poynter ME
AUID- ORCID: 0000-0002-7578-4570
AD  - Department of Medicine, University of Vermont, Burlington, Vermont.
FAU - Dixon, Anne E
AU  - Dixon AE
AD  - Department of Medicine, University of Vermont, Burlington, Vermont.
FAU - Anathy, Vikas
AU  - Anathy V
AUID- ORCID: 0000-0003-4288-912X
AD  - Department of Pathology and Laboratory Medicine, University of Vermont, 
      Burlington, Vermont.
LA  - eng
GR  - R01 HL136917/HL/NHLBI NIH HHS/United States
GR  - P20 GM103449/GM/NIGMS NIH HHS/United States
GR  - T32 HL076122/HL/NHLBI NIH HHS/United States
GR  - R01 HL138708/HL/NHLBI NIH HHS/United States
GR  - R01 HL141364/HL/NHLBI NIH HHS/United States
GR  - R01 HL142081/HL/NHLBI NIH HHS/United States
GR  - S10 OD025030/OD/NIH HHS/United States
GR  - R01 HL122383/HL/NHLBI NIH HHS/United States
GR  - R01 HL133920/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20221213
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 47BYS17IY0 (mitoquinone)
RN  - 37107-08-7 (DTPP)
SB  - IM
MH  - Animals
MH  - *Asthma/metabolism
MH  - Lung/metabolism
MH  - Obesity/metabolism
MH  - Inflammation/pathology
MH  - Pyroglyphidae
MH  - *Eosinophilia/pathology
MH  - Disease Models, Animal
PMC - PMC9902225
OTO - NOTNLM
OT  - ER stress
OT  - MitoQ
OT  - obese allergic asthma
COIS- Y. Janssen-Heininger and V. Anathy hold patents: United States Patent No. 
      8,679,811, "Treatments Involving Glutaredoxins and Similar Agents"; United States 
      Patent No. 8,877,447, "Detection of Glutathionylated Proteins"; United States 
      Patent Nos. 9,907,828 and 10,688,150, "Treatments of oxidative stress 
      conditions." In the past, Y. Janssen-Heininger and V. Anathy have received 
      consulting fees and laboratory contracts from Celdara Medical LLC, NH. None of 
      the other authors has any conflicts of interest, financial or otherwise, to 
      disclose.
EDAT- 2022/12/14 06:00
MHDA- 2023/02/09 06:00
PMCR- 2024/02/01
CRDT- 2022/12/13 08:03
PHST- 2022/12/14 06:00 [pubmed]
PHST- 2023/02/09 06:00 [medline]
PHST- 2022/12/13 08:03 [entrez]
PHST- 2024/02/01 00:00 [pmc-release]
AID - L-00249-2022 [pii]
AID - 10.1152/ajplung.00249.2022 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2023 Feb 1;324(2):L141-L153. doi: 
      10.1152/ajplung.00249.2022. Epub 2022 Dec 13.