The Library
PKG1α oxidation negatively regulates food seeking behaviour and reward
Tools
Duraffourd, Celine, Huckstepp, Robert T. R., Braren, Ingke, Fernandes, Cathy, Brock, Olivier, Delogu, Alessio, Prysyazhna, Oleksandra, Burgoyne, Joseph and Eaton, Philip (2019) PKG1α oxidation negatively regulates food seeking behaviour and reward. Redox Biology, 21 . 101077. doi:10.1016/j.redox.2018.101077 ISSN 2213-2317.
|
PDF
WRAP-PKG1a-oxidation-regulates-food-reward-Huckstepp-2018.pdf - Accepted Version - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (9Mb) | Preview |
Official URL: https://doi.org/10.1016/j.redox.2018.101077
Abstract
Genes that are highly conserved in food seeking behaviour, such as protein kinase G (PKG), are of interest because of their potential role in the global obesity epidemic. PKG1α can be activated by binding of cyclic guanosine monophosphate (cGMP) or oxidant-induced interprotein disulfide bond formation between the two subunits of this homodimeric kinase. PKG1α activation by cGMP plays a role in reward and addiction through its actions in the ventral tegmental area (VTA) of the brain. ‘Redox dead’ C42S PKG1α knock-in (KI) mice, which are fully deficient in oxidant- induced disulfide-PKG1α formation, display increased food seeking and reward behaviour compared to wild-type (WT) littermates. Rewarding monoamines such as dopamine, which are released during feeding, are metabolised by monoamine oxidase to generate hydrogen peroxide that was shown to mediate PKG1α oxidation. Indeed, inhibition of monoamine oxidase, which prevents it producing hydrogen peroxide, attenuated PKG1α oxidation and increased sucrose preference in WT, but not KI mice. The deficient reward phenotype of the KI mice was rescued by expressing WT kinase that can form the disulfide state in the VTA using an adeno-associated virus, consistent with PKG1α oxidation providing a break on feeding behaviour. In conclusion, disulfide-PKG1α in VTA neurons acts as a negative regulator of feeding and therefore may provide a novel therapeutic target for obesity.
Item Type: | Journal Article | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
|||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Obesity -- Genetics, Protein kinases, Cyclic guanylic acid, Dopamine | |||||||||||||||
Journal or Publication Title: | Redox Biology | |||||||||||||||
Publisher: | Elsevier | |||||||||||||||
ISSN: | 2213-2317 | |||||||||||||||
Official Date: | February 2019 | |||||||||||||||
Dates: |
|
|||||||||||||||
Volume: | 21 | |||||||||||||||
Article Number: | 101077 | |||||||||||||||
DOI: | 10.1016/j.redox.2018.101077 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 11 December 2018 | |||||||||||||||
Date of first compliant Open Access: | 11 December 2018 | |||||||||||||||
RIOXX Funder/Project Grant: |
|
|||||||||||||||
Related URLs: |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year