SERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin-deficient mice.

08:00 EDT 1st August 2019 | BioPortfolio

Summary of "SERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin-deficient mice."

The sarco/endoplasmic reticulum Ca -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 (Taz ) 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 Taz LV, a result that correlated with elevated SERCA2a tyrosine nitration. In addition PLN protein was decreased, and its phosphorylation was increased in Taz 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 Taz mice. Nonetheless, we demonstrate for the first time that SERCA function is impaired in LVs obtained from young and old Taz mice likely due to elevated ROS/RNS production. Future studies should determine whether improving SERCA function can improve cardiac contractility and pathology in Taz mice.


Journal Details

This article was published in the following journal.

Name: Physiological reports
ISSN: 2051-817X
Pages: e14215


DeepDyve research library

PubMed Articles [2523 Associated PubMed Articles listed on BioPortfolio]

Evidence for the Prerequisite Formation of Phenoxyl Radical in Radical-Mediated Peptide Tyrosine Nitration In Vacuo.

Elementary mechanism of radical-mediated peptide tyrosine nitration-a hallmark of post-translational modification of proteins under nitrative stress in vivo -has been elucidated in detail using an int...

Mechanistic insight into the catalytic inhibition by nitroxides of tyrosine oxidation and nitration.

Nitroxide antioxidants (RNO) protect from injuries associated with oxidative stress. Tyrosine residues in proteins are major targets for oxidizing species giving rise to irreversible cross-linking and...

Newly Discovered Micropeptide Regulators of SERCA Form Oligomers but Bind to the Pump as Monomers.

The recently-discovered single-span transmembrane proteins endoregulin (ELN), dwarf open reading frame (DWORF), myoregulin (MLN), and another-regulin (ALN) are reported to bind to the SERCA calcium pu...

Structure effect of water-soluble iron porphyrins on catalyzing protein tyrosine nitration in the presence of nitrite and hydrogen peroxide.

Water-soluble iron porphyrins, such as FeTPPS (5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III)), FeTMPyP (5,10,15,20-tetrakis (N-methyl-4'-pyridyl) porphyrinato iron (III) chloride) an...

Structural Basis of Sarco/Endoplasmic Reticulum Ca-ATPase 2b Regulation via Transmembrane Helix Interplay.

Sarco/endoplasmic reticulum (ER) Ca-ATPase 2b (SERCA2b) is a ubiquitously expressed membrane protein that facilitates Ca uptake from the cytosol to the ER. SERCA2b includes a characteristic 11 transme...

Clinical Trials [1545 Associated Clinical Trials listed on BioPortfolio]

SERCA Gene Therapy Trial

The aim of the study is to determine the safety and feasibility of giving an adeno-associated viral vector expressing the sarcoplasmic reticulum calcium ATPase (SERCA2a), driven by the CMV...

Ventricular Arrhythmias in Uremic Cardiomyopathy

There is a certain gene called sarcoplasmic reticulum gene (SERCA2a), which is found in heart muscle. This gene is also found in blood vessels and skin tissue. When active this gene builds...

Tyrosine for Methamphetamine Dependence - 1

The purpose of this study is to evaluate efficacy of tyrosine as a treatment for methamphetamine dependence in an outpatient treatment setting providing group psychosocial interventions. ...

Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a

Heart failure with preserved ejection fraction or HFpEF, represents nearly 50% of all heart failure cases and is particularly common in the elderly. The disease has no current treatment op...

The Effect of Exercise on Muscle Dysfunction in Cystinosis

Classification of activity tolerance is of importance in chronic progressive myopathies, not only to better understand functional implications of the disease state itself, but also for pur...

Medical and Biotech [MESH] Definitions

A respiratory function test that includes the maximal inspiratory pressure and maximal expiratory pressure. It is determined by SPIROMETRY that measures the patient's RESIDUAL VOLUME and TOTAL LUNG CAPACITY and assesses the strength of RESPIRATORY MUSCLES.

The volume of air that is exhaled by a maximal expiration following a maximal inspiration.

Wide continuum of associated cognitive and neurobehavioral disorders, including, but not limited to, three core-defining features: impairments in socialization, impairments in verbal and nonverbal communication, and restricted and repetitive patterns of behaviors. (from DSM-V)

The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an EXERCISE TEST.

A metabolic excess of REACTIVE NITROGEN SPECIES, including NITRIC OXIDE and PEROXYNITRITE, that leads to damaging effects of oxidation and nitration.

Quick Search

DeepDyve research library

Relevant Topics

Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...

Stress is caused by your perception of situations around you and then the reaction of your body to them. The automatic stress response to unexpected events is known as 'fight or flight'. Discovered by Walter Cannon in 1932, it is the release of h...

Searches Linking to this Article