TY  - JOUR
A1  - Szibor, Marten
A1  - Schreckenberg, Rolf
A1  - Gizatullina, Zemfira
A1  - Dufour, Eric
A1  - Wiesnet, Marion
A1  - Dhandapani, Praveen K.
A1  - Debska‐Vielhaber, Grazyna
A1  - Heidler, Juliana
A1  - Wittig, Ilka
A1  - Nyman, Tuula A.
A1  - Gärtner, Ulrich
A1  - Hall, Andrew R.
A1  - Pell, Victoria
A1  - Viscomi, Carlo
A1  - Krieg, Thomas
A1  - Murphy, Michael P.
A1  - Braun, Thomas
A1  - Gellerich, Frank Norbert
A1  - Schlüter, Klaus‐Dieter
A1  - Jacobs, Howard T.
T1  - Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia
T2  - Journal of cellular and molecular medicine
N2  - Cardiac ischaemia‐reperfusion (I/R) injury has been attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which include redox imbalance, metabolic stalling and excessive production of reactive oxygen species (ROS). The alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool to reduce oxygen to water, thereby restoring electron flux when impaired and, in the process, blunting ROS production. Hence, AOX represents a natural rescue mechanism from respiratory stress. This study aimed to determine how respiratory restoration through xenotopically expressed AOX affects the re‐perfused post‐ischaemic mouse heart. As expected, AOX supports ETC function and attenuates the ROS load in post‐anoxic heart mitochondria. However, post‐ischaemic cardiac remodelling over 3 and 9 weeks was not improved. AOX blunted transcript levels of factors known to be up‐regulated upon I/R such as the atrial natriuretic peptide (Anp) whilst expression of pro‐fibrotic and pro‐apoptotic transcripts were increased. Ex vivo analysis revealed contractile failure at nine but not 3 weeks after ischaemia whilst label‐free quantitative proteomics identified an increase in proteins promoting adverse extracellular matrix remodelling. Together, this indicates an essential role for ETC‐derived signals during cardiac adaptive remodelling and identified ROS as a possible effector.
KW  - adaptive cardiac remodelling
KW  - alternative oxidase
KW  - cardiac ischaemia‐reperfusion
KW  - electron transport chain
KW  - mouse
KW  - reactive oxygen species
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57078
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-570787
SN  - 1582-4934
VL  - 24
IS  - 6
SP  - 3534
EP  - 3548
PB  - Wiley-Blackwell
CY  - Hoboken, NJ
ER  -