Deletion of ASK1 Protects against Hyperoxia-Induced Acute Lung Injury

PloS One
Jutaro FukumotoNarasaiah Kolliputi

Abstract

Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAPK kinase kinase kinase (MAP3K) family, is activated by various stimuli, which include oxidative stress, endoplasmic reticulum (ER) stress, calcium influx, DNA damage-inducing agents and receptor-mediated signaling through tumor necrosis factor receptor (TNFR). Inspiration of a high concentration of oxygen is a palliative therapy which counteracts hypoxemia caused by acute lung injury (ALI)-induced pulmonary edema. However, animal experiments so far have shown that hyperoxia itself could exacerbate ALI through reactive oxygen species (ROS). Our previous data indicates that ASK1 plays a pivotal role in hyperoxia-induced acute lung injury (HALI). However, it is unclear whether or not deletion of ASK1 in vivo protects against HALI. In this study, we investigated whether ASK1 deletion would lead to attenuation of HALI. Our results show that ASK1 deletion in vivo significantly suppresses hyperoxia-induced elevation of inflammatory cytokines (i.e. IL-1β and TNF-α), cell apoptosis in the lung, and recruitment of immune cells. In summary, the results from the study suggest that deletion of ASK1 in mice significantly inhibits hyperoxic lung injury.

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Citations

Feb 2, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Venkata Ramireddy NaralaNarasaiah Kolliputi
Feb 17, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yan YeMin Wu
Jul 8, 2016·American Journal of Physiology. Cell Physiology·Mason BreitzigNarasaiah Kolliputi
Apr 19, 2018·American Journal of Physiology. Cell Physiology·Mason T BreitzigNarasaiah Kolliputi
Jan 11, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Camille N ImmanuelChristopher M Waters
Mar 31, 2018·Oxidative Medicine and Cellular Longevity·Lei ZhangLin Wang
Feb 19, 2021·Frontiers in Pharmacology·Sahebgowda Sidramagowda PatilLakshmi Galam
Mar 27, 2021·Frontiers in Medicine·Luciano AmarelleLeonel Malacrida

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Methods Mentioned

BETA
transmission electron microscopy
bronchoalveolar lavage
ELISA
lavage

Software Mentioned

GraphPad
GraphPad Prism

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