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
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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