Cysteine hydropersulfide reduces lipid peroxidation and protects against myocardial ischaemia-reperfusion injury - Are endogenous persulfides mediators of ischaemic preconditioning?
Cysteine hydropersulfide reduces lipid peroxidation and protects against myocardial ischaemia-reperfusion injury - Are endogenous persulfides mediators of ischaemic preconditioning?
Earlier studies revealed the presence of cysteine persulfide (CysSSH) and related polysulfide species in various mammalian tissues. CysSSH has both antioxidant and oxidant properties, modulates redox-dependent signal transduction and has been shown to mitigate oxidative stress. However, its functional relevance in the setting of myocardial ischaemia-reperfusion injury (IRI) remains unknown. The present study was undertaken to (1) study the dynamics of production and consumption of persulfides under normoxic and hypoxic conditions in the heart, and (2) determine whether exogenous administration of the CysSSH donor, cysteine trisulfide (Cys-SSS-Cys) at the onset of reperfusion rescues functional impairment and myocardial damage by interfering with lipid peroxidation. Utilising a well-established ex vivo Langendorff murine model, we here demonstrate that endogenous tissue concentrations of CysSSH are upregulated when oxygen supply is compromised (global myocardial ischaemia) and rapidly restored to baseline levels upon reperfusion, suggestive of active regulation. In a separate set of experiments, exogenous administration of Cys-SSS-Cys for 10 min at the onset of reperfusion was found to decrease malondialdehyde (MDA) concentrations, formation of 4-hydroxynonenal (4-HNE) protein adducts and rescue the heart from injury. Cys-SSS-Cys also restored post-ischaemic cardiac function, improving both coronary flow and left ventricular developed pressure (LVDP). Taken together, these results support the notion that endogenous CysSSH plays an important role as a "redox preconditioning" agent to combat the oxidative insult in myocardial IRI.
Animals, Cysteine/metabolism, Ischemic Preconditioning, Ischemic Preconditioning, Myocardial, Lipid Peroxidation, Mammals/metabolism, Mice, Myocardial Reperfusion Injury/prevention & control, Myocardium/metabolism
102605
Griffiths, Kayleigh
0a807d8e-54aa-4c82-b5e7-3656cde837fd
Ida, Tomoaki
ebbb63cc-ecd5-4ac7-b3c0-04c6df0963f9
Morita, Masanobu
3a0bc194-e18d-4f9f-9ab0-b64390594be5
Lamb, Reece J
336f4f16-16dd-4728-9c69-ed998102da00
Lee, Jordan J
3f24f9f8-1acb-4cf7-aa10-783dfeaecab4
Frenneaux, Michael P
82824b6d-51f1-4b31-9f7a-5b4746d59833
Fukuto, Jon M
222058bd-beef-4b4e-856c-54b1fc7eb4a9
Akaike, Takaaki
3d8928b7-533c-4fd7-b588-dc709f592ba1
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Madhani, Melanie
63a48cca-67b7-41ae-bc79-0f4a166f0750
1 April 2023
Griffiths, Kayleigh
0a807d8e-54aa-4c82-b5e7-3656cde837fd
Ida, Tomoaki
ebbb63cc-ecd5-4ac7-b3c0-04c6df0963f9
Morita, Masanobu
3a0bc194-e18d-4f9f-9ab0-b64390594be5
Lamb, Reece J
336f4f16-16dd-4728-9c69-ed998102da00
Lee, Jordan J
3f24f9f8-1acb-4cf7-aa10-783dfeaecab4
Frenneaux, Michael P
82824b6d-51f1-4b31-9f7a-5b4746d59833
Fukuto, Jon M
222058bd-beef-4b4e-856c-54b1fc7eb4a9
Akaike, Takaaki
3d8928b7-533c-4fd7-b588-dc709f592ba1
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Madhani, Melanie
63a48cca-67b7-41ae-bc79-0f4a166f0750
Griffiths, Kayleigh, Ida, Tomoaki, Morita, Masanobu, Lamb, Reece J, Lee, Jordan J, Frenneaux, Michael P, Fukuto, Jon M, Akaike, Takaaki, Feelisch, Martin and Madhani, Melanie
(2023)
Cysteine hydropersulfide reduces lipid peroxidation and protects against myocardial ischaemia-reperfusion injury - Are endogenous persulfides mediators of ischaemic preconditioning?
Redox Biology, 60, , [102605].
(doi:10.1016/j.redox.2023.102605).
Abstract
Earlier studies revealed the presence of cysteine persulfide (CysSSH) and related polysulfide species in various mammalian tissues. CysSSH has both antioxidant and oxidant properties, modulates redox-dependent signal transduction and has been shown to mitigate oxidative stress. However, its functional relevance in the setting of myocardial ischaemia-reperfusion injury (IRI) remains unknown. The present study was undertaken to (1) study the dynamics of production and consumption of persulfides under normoxic and hypoxic conditions in the heart, and (2) determine whether exogenous administration of the CysSSH donor, cysteine trisulfide (Cys-SSS-Cys) at the onset of reperfusion rescues functional impairment and myocardial damage by interfering with lipid peroxidation. Utilising a well-established ex vivo Langendorff murine model, we here demonstrate that endogenous tissue concentrations of CysSSH are upregulated when oxygen supply is compromised (global myocardial ischaemia) and rapidly restored to baseline levels upon reperfusion, suggestive of active regulation. In a separate set of experiments, exogenous administration of Cys-SSS-Cys for 10 min at the onset of reperfusion was found to decrease malondialdehyde (MDA) concentrations, formation of 4-hydroxynonenal (4-HNE) protein adducts and rescue the heart from injury. Cys-SSS-Cys also restored post-ischaemic cardiac function, improving both coronary flow and left ventricular developed pressure (LVDP). Taken together, these results support the notion that endogenous CysSSH plays an important role as a "redox preconditioning" agent to combat the oxidative insult in myocardial IRI.
This record has no associated files available for download.
More information
Accepted/In Press date: 9 January 2023
e-pub ahead of print date: 17 January 2023
Published date: 1 April 2023
Additional Information:
Funding Information:
This work was funded by the British Heart Foundation ( PG/19/87/34792 ) awarded to M.M, M.P.F and MF. Grants-in-Aid for Scientific Research [(S), (A), (B), (C), Challenging Exploratory Research, Transformative Research Areas] from the Ministry of Education, Culture, Sports, Science and Technology, Japan , to T.A ( 18H05277 , 20K21496 and 21H05263 ), T.I ( 20K07306 ), and M.Mo ( 19K07341 ); Japan Science and Technology ( S22098 ), CREST Grant Number JPMJCR2024 , Japan, to T.A; Japan Agency for Medical Research and Development (AMED) Grant Number JP21zf0127001 , Japan, to T.A. Japan Society for the Promotion of Science Invitational Fellowship awarded to M.M ( s22098 ).
Publisher Copyright:
© 2023 The Authors
Keywords:
Animals, Cysteine/metabolism, Ischemic Preconditioning, Ischemic Preconditioning, Myocardial, Lipid Peroxidation, Mammals/metabolism, Mice, Myocardial Reperfusion Injury/prevention & control, Myocardium/metabolism
Identifiers
Local EPrints ID: 475948
URI: http://eprints.soton.ac.uk/id/eprint/475948
ISSN: 2213-2317
PURE UUID: 19b77137-dc89-4b3b-be80-a7181f0870aa
Catalogue record
Date deposited: 31 Mar 2023 16:51
Last modified: 17 Mar 2024 03:27
Export record
Altmetrics
Contributors
Author:
Kayleigh Griffiths
Author:
Tomoaki Ida
Author:
Masanobu Morita
Author:
Reece J Lamb
Author:
Jordan J Lee
Author:
Michael P Frenneaux
Author:
Jon M Fukuto
Author:
Takaaki Akaike
Author:
Melanie Madhani
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
