Show simple item record

dc.contributor.authorBraun, Jessica L.
dc.contributor.authorHamstra, Sophie I.
dc.contributor.authorMessner, Holt N.
dc.contributor.authorFajardo, Val A.
dc.date.accessioned2019-08-27T14:02:31Z
dc.date.available2019-08-27T14:02:31Z
dc.date.issued2019-08
dc.identifier.citationPhysiol Rep. 2019 Aug;7(16):e14215. doi: 10.14814/phy2.14215.en_US
dc.identifier.issn2051-817X
dc.identifier.urihttp://hdl.handle.net/10464/14479
dc.description.abstractThe sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) is imperative for normal cardiac function regulating both muscle relaxation and contractility. SERCA2a is the predominant isoform in cardiac muscles and is inhibited by phospholamban (PLN). Under conditions of oxidative stress, SERCA2a may also be impaired by tyrosine nitration. Tafazzin (Taz) is a mitochondrial specific transacylase that regulates mature cardiolipin (CL) formation, and its absence leads to mitochondrial dysfunction and excessive production of reactive oxygen/nitrogen species (ROS/RNS). In the present study, we examined SERCA function, SERCA2a tyrosine nitration, and PLN expression/phosphorylation in left ventricles (LV) obtained from young (3-5 months) and old (10-12 months) wild-type (WT) and Taz knockdown (TazKD) male mice. These mice are a mouse model for Barth syndrome, which is characterized by mitochondrial dysfunction, excessive ROS/RNS production, and dilated cardiomyopathy (DCM). Here, we show that maximal SERCA activity was impaired in both young and old TazKD LV, a result that correlated with elevated SERCA2a tyrosine nitration. In addition PLN protein was decreased, and its phosphorylation was increased in TazKD LV compared with control, which suggests that PLN may not contribute to the impairments in SERCA function. These changes in expression and phosphorylation of PLN may be an adaptive response aimed to improve SERCA function in TazKD mice. Nonetheless, we demonstrate for the first time that SERCA function is impaired in LVs obtained from young and old TazKD mice likely due to elevated ROS/RNS production. Future studies should determine whether improving SERCA function can improve cardiac contractility and pathology in TazKD miceen_US
dc.description.sponsorshipBrock University Library Open Access Publishing Funden_US
dc.language.isoenen_US
dc.publisherThe Physiological Societyen_US
dc.subjectCa2+ regulationen_US
dc.subjectphospholambanen_US
dc.subjectdilated cardiomyopathyen_US
dc.titleSERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin deficient miceen_US
dc.identifier.doi10.14814/phy2.14215


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record