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dc.contributor.authorHausenloy, DJ
dc.contributor.authorLim, SY
dc.contributor.authorOng, S-G
dc.contributor.authorDavidson, SM
dc.contributor.authorYellon, DM
dc.date.accessioned2021-02-04T00:49:44Z
dc.date.available2021-02-04T00:49:44Z
dc.date.issued2010-10-01
dc.identifierpii: cvq113
dc.identifier.citationHausenloy, D. J., Lim, S. Y., Ong, S. -G., Davidson, S. M. & Yellon, D. M. (2010). Mitochondrial cyclophilin-D as a critical mediator of ischaemic preconditioning.. Cardiovasc Res, 88 (1), pp.67-74. https://doi.org/10.1093/cvr/cvq113.
dc.identifier.issn0008-6363
dc.identifier.urihttp://hdl.handle.net/11343/259202
dc.description.abstractAIMS: It has been suggested that mitochondrial reactive oxygen species (ROS), Akt and Erk1/2 and more recently the mitochondrial permeability transition pore (mPTP) may act as mediators of ischaemic preconditioning (IPC), although the actual interplay between these mediators is unclear. The aim of the present study is to determine whether the cyclophilin-D (CYPD) component of the mPTP is required by IPC to generate mitochondrial ROS and subsequently activate Akt and Erk1/2. METHODS AND RESULTS: Mice lacking CYPD (CYPD-/-) and B6Sv129 wild-type (WT) mice were used throughout. We have demonstrated that under basal conditions, non-pathological mPTP opening occurs (indicated by the percent reduction in mitochondrial calcein fluorescence). This effect was greater in WT cardiomyocytes compared with CYPD-/- ones (53 ± 2% WT vs. 17 ± 3% CYPD-/-; P < 0.01) and was augmented by hypoxic preconditioning (HPC) (70 ± 9% WT vs. 56 ± 1% CYPD-/-; P < 0.01). HPC reduced cell death following simulated ischaemia-reperfusion injury in WT (23.2 ± 3.5% HPC vs. 43.7 ± 3.2% WT; P < 0.05) but not CYPD-/- cardiomyocytes (19.6 ± 1.4% HPC vs. 24.4 ± 2.6% control; P > 0.05). HPC generated mitochondrial ROS in WT (four-fold increase; P < 0.05) but not CYPD-/- cardiomyocytes. HPC induced significant Akt phosphorylation in WT cardiomyocytes (two-fold increase; P < 0.05), an effect which was abrogated by ciclosporin-A (a CYPD inhibitor) and N-2-mercaptopropionyl glycine (a ROS scavenger). Finally, in vivo IPC of adult murine hearts resulted in significant phosphorylation of Akt and Erk1/2 in WT but not CYPD-/- hearts. CONCLUSION: The CYPD component of the mPTP is required by IPC to generate mitochondrial ROS and phosphorylate Akt and Erk1/2, major steps in the IPC signalling pathway.
dc.languageeng
dc.publisherOxford University Press (OUP)
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0
dc.titleMitochondrial cyclophilin-D as a critical mediator of ischaemic preconditioning.
dc.typeJournal Article
dc.identifier.doi10.1093/cvr/cvq113
melbourne.affiliation.departmentSurgery (St Vincent's)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleCardiovascular Research
melbourne.source.volume88
melbourne.source.issue1
melbourne.source.pages67-74
dc.rights.licenseCC BY-NC
melbourne.elementsid1207289
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936122
melbourne.contributor.authorLim, Shiang
dc.identifier.eissn1755-3245
melbourne.accessrightsOpen Access


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