Document Detail


BAS/BSCR15 The role of PINK1, a mitochondrial pro-survival kinase, in myocardial ischaemia-reperfusion.
MedLine Citation:
PMID:  20801804     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
PINK1, a kinase localised mainly in mitochondria, can protect neurons against oxidative damage and apoptosis by maintaining mitochondrial structure and function. Although PINK1 is highly expressed in the myocardium, there are no studies investigating the role of this kinase in the heart. We hypothesised that PINK1 could protect cardiomyocytes from ischaemia-reperfusion (I-R) injury and therefore, PINK1 downregulation would be detrimental to the ischaemic-reperfused heart. Hearts isolated from PINK1+/+, PINK1+/- and PINK1-/- mice were perfused in a Langendorff constant pressure system and subjected to 35 min global normothermic ischaemia and 30 min reperfusion. Infarct size was measured, using triphenyltetrazolium chloride (TTC) staining, and expressed as percentage of the myocardium at risk (I/R%). Electron microscopy was used to investigate ultrastructural changes in cardiomyocytes, and the expression of autophagic markers such as Beclin1 and LC3b was measured in PINK1-/- hearts. Our data show that the PINK1 KO hearts develop significantly larger infarctions following lethal ischaemia and reperfusion (25.1+/-1.97% in PINK1+/+ hearts vs 38.9+/-3.42% (p<0.01) and 51.5+/-4.3% (p<0.001) in PINK1+/- and PINK1-/- hearts, respectively). Interestingly, electron microscopic images showed significantly more vacuole-like structures that contained cellular material (indicative of autophagy) in PINK1-/- hearts. We further observed that PINK1-/- hearts had significantly more Beclin1 and total LC3b than hearts from PINK1+/+ littermate controls (Beclin1: 0.674+/-0.065 in PINK1+/+ vs 0.85+/-0.019 in PINK1-/- hearts, p<0.05) total LC3b: 0.946+/-0.139 in PINK1+/+ vs 1.445+/-0.141 in PINK1-/- hearts, p<0.05; values are in arbitrary units of densitometry). In conclusion, our results suggest that during ischaemic-reperfusion PINK1 acts as an endogenous protective kinase with the regulation of mitophagy being a possible mechanism of its protection.
Authors:
H Siddall; R Sands; S M Davidson; D J Hausenloy; M M Mocanu; D M Yellon
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Heart (British Cardiac Society)     Volume:  96     ISSN:  1468-201X     ISO Abbreviation:  Heart     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9602087     Medline TA:  Heart     Country:  England    
Other Details:
Languages:  eng     Pagination:  e16-7     Citation Subset:  AIM; IM    
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