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The Role of DJ-1 in Cardioprotection

Mukherjee, UA; (2013) The Role of DJ-1 in Cardioprotection. Doctoral thesis , UCL (University College London).

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Abstract

Background Mutations in the DJ-1 gene in dopaminergic neurones induce mitochondrial dysfunction and a genetic form of Parkinson’s disease (PD). Although DJ-1 is present in the heart its role there is currently unknown. We hypothesised that DJ-1 may be a novel target for cardioprotection. Methods and Results Overexpression of wild-type (WT) DJ-1 in the HL-1 cardiac cell line induced mitochondrial elongation, delayed the opening of the mitochondrial permeability transition pore (mPTP), and reduced cell death following simulated ischaemia-reperfusion injury (s I/R), effects which were absent in non-functional DJ-1 mutants. Adult murine hearts deficient in DJ-1 sustained larger myocardial infarcts following in vivo 45 minutes regional ischaemia and 24 hours reperfusion, and were partially resistant to ischaemic preconditioning (IPC), when compared to WT controls. DJ-1 deficient murine hearts displayed increased mitochondrial fragmentation, although there were no differences in mitochondrial function, myocardial ATP levels, or cardiac dimensions or function. Conclusion DJ-1 is a novel target for cardioprotection.

Type: Thesis (Doctoral)
Title: The Role of DJ-1 in Cardioprotection
Language: English
Additional information: Permission for digitisation has not been received.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
URI: https://discovery.ucl.ac.uk/id/eprint/1389937
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