Asset Details
Do you wish to reserve the book?
Macrophage achieves self-protection against oxidative stress-induced ageing through the Mst-Nrf2 axis
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Macrophage achieves self-protection against oxidative stress-induced ageing through the Mst-Nrf2 axis
Do you wish to request the book?
Macrophage achieves self-protection against oxidative stress-induced ageing through the Mst-Nrf2 axis
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Macrophage achieves self-protection against oxidative stress-induced ageing through the Mst-Nrf2 axis
2019
Overview
Reactive oxygen species (ROS) production in phagocytes is a major defense mechanism against pathogens. However, the cellular self-protective mechanism against such potential damage from oxidative stress remains unclear. Here we show that the kinases Mst1 and Mst2 (Mst1/2) sense ROS and maintain cellular redox balance by modulating the stability of antioxidant transcription factor Nrf2. Site-specific ROS release recruits Mst1/2 from the cytosol to the phagosomal or mitochondrial membrane, with ROS subsequently activating Mst1/2 to phosphorylate kelch like ECH associated protein 1 (Keap1) and prevent Keap1 polymerization, thereby blocking Nrf2 ubiquitination and degradation to protect cells against oxidative damage. Treatment with the antioxidant N-acetylcysteine disrupts ROS-induced interaction of Mst1/2 with phagosomes or mitochondria, and thereby diminishes the Mst-Nrf2 signal. Consistently, loss of Mst1/2 results in increased oxidative injury, phagocyte ageing and death. Thus, our results identify the Mst-Nrf2 axis as an important ROS-sensing and antioxidant mechanism during an antimicrobial response.
Immune cells produce reactive oxygen species (ROS) to eliminate pathogens, but cell-spontaneous death and ageing may also be induced. Here the authors show that, upon sensing ROS, Mst1/2 kinases modulate the activity of Nrf2 transcription factor and downstream genetic programs to protect mouse macrophages from death and ageing.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 96
/ Aging
/ Animals
/ Cytosol
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Mice
/ NF-E2-Related Factor 2 - genetics
/ NF-E2-Related Factor 2 - metabolism
/ Protein-Serine-Threonine Kinases - genetics
/ Protein-Serine-Threonine Kinases - metabolism
/ Proteins
/ Reactive Oxygen Species - metabolism
/ Science
