SERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin-deficient mice
Autor: | Val A. Fajardo, Jessica L. Braun, Holt N. Messner, Sophie I. Hamstra |
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Rok vydání: | 2019 |
Předmět: |
Male
medicine.medical_specialty SERCA Ca2+ regulation Physiology Heart Ventricles Tafazzin 030204 cardiovascular system & hematology medicine.disease_cause lcsh:Physiology Sarcoplasmic Reticulum Calcium-Transporting ATPases Signalling Pathways Contractility 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Physiology (medical) Internal medicine Cardiac Muscle medicine Cardiolipin Animals phospholamban Original Research biology lcsh:QP1-981 Chemistry Calcium-Binding Proteins Barth syndrome Heart medicine.disease Phospholamban dilated cardiomyopathy Disease Models Animal Oxidative Stress Endocrinology Gene Knockdown Techniques Barth Syndrome biology.protein cardiovascular system Phosphorylation Tyrosine Endocrine and Metabolic Conditons Disorders and Treatments Muscle Contraction and Relaxation 030217 neurology & neurosurgery Oxidative stress Acyltransferases Transcription Factors |
Zdroj: | Physiological Reports Physiological Reports, Vol 7, Iss 16, Pp n/a-n/a (2019) |
ISSN: | 2051-817X |
Popis: | The 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 mice. |
Databáze: | OpenAIRE |
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