A5028295383- Mitochondrial Function and Pathology
- Neurobiology and Insect Physiology Research
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Cardiac Ischemia and Reperfusion
- Retinal Development and Disorders
- ATP Synthase and ATPases Research
- Physiological and biochemical adaptations
- RNA Research and Splicing
- Hormonal Regulation and Hypertension
- Cardiomyopathy and Myosin Studies
- Animal Behavior and Reproduction
- Photoreceptor and optogenetics research
- Nitric Oxide and Endothelin Effects
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Neuroscience and Neural Engineering
- Cardiovascular Function and Risk Factors
- Phosphodiesterase function and regulation
- Receptor Mechanisms and Signaling
- Parkinson's Disease Mechanisms and Treatments
- Cancer-related gene regulation
- Protein Kinase Regulation and GTPase Signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Plant and Biological Electrophysiology Studies
University of Iowa
2012-2024
Institute of Molecular Biology and Biophysics
2018
Iowa City VA Health Care System
2013
The Ohio State University
2012
University of California, Los Angeles
2012
Cornell University
2002
Florida Atlantic University
2002
Brandeis University
1997-2000
Cumulative oxidative damages to cell constituents are considered contribute aging and age-related diseases. The enzyme peptide methionine sulfoxide reductase A (MSRA) catalyzes the repair of oxidized in proteins by reducing back methionine. However, whether MSRA plays a role process is poorly understood. Here we report that overexpression msrA gene predominantly nervous system markedly extends lifespan fruit fly Drosophila . transgenic animals more resistant paraquat-induced stress, onset...
Sinus node dysfunction (SND) is a major public health problem that associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little known about the molecular cellular mechanisms cause SND. Most SND occurs in setting heart failure hypertension, conditions are marked by elevated circulating angiotensin II (Ang II) increased oxidant stress. Here, we show oxidized calmodulin kinase (ox-CaMKII) biomarker for patients dogs disease determinant mice....
Significance Mitochondrial Ca 2+ is a fundamental signal that allows for adaptation to physiological stress but liability during ischemia-reperfusion injury in heart. On one hand, mitochondrial entry coordinates energy supply and demand myocardium by increasing the activity of matrix dehydrogenases augment ATP production oxidative phosphorylation. other inhibiting overload promulgated as therapeutic approach preserve myocardial tissue following injury. We developed new mouse model...
Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart resistant current therapies. However, the metabolic mechanisms driving acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates entry into matrix stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of dominant-negative (DN) MCU. Here, we show that DN-MCU had normal resting rates...
Abstract Despite the clear association between myocardial injury, heart failure and depressed energetics, little is known about upstream signals responsible for remodeling metabolism after pathological stress. Here, we report increased mitochondrial calmodulin kinase II (CaMKII) activation left ventricular dilation in mice one week infarction (MI) surgery. By contrast, with genetic CaMKII inhibition are protected from dysfunction MI. Mice overexpression (mtCaMKII) have severe dilated...
Inhibition of the multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) or depletion sarcoplasmic reticulum (SR) Ca(2+) stores protects against apoptosis from excessive isoproterenol (Iso) stimulation in cultured ventricular myocytes, suggesting that CaMKII inhibition could be a novel approach to reducing cell death conditions increased adrenergic tone, such as myocardial infarction (MI), vivo. We used mice with genetic due transgenic expression highly specific inhibitory...
Excessive activation of calmodulin kinase II (CaMKII) causes arrhythmias and heart failure, but the cellular mechanisms for CaMKII-targeted proteins causing disordered cell membrane excitability myocardial dysfunction remain uncertain. Failing human cardiomyocytes exhibit increased CaMKII voltage-gated Ca 2+ channel (Ca V 1.2) activity, enhanced expression a specific 1.2 β-subunit protein isoform ( β 2a ). We recently identified residues critical phosphorylation (Thr 498) binding (Leu 493),...
α<sub>2</sub>δ-4 is an auxiliary subunit of voltage-gated Ca<sub>v</sub>1.4 L-type channels that regulate the development and mature exocytotic function photoreceptor ribbon synapse. In humans, mutations in <i>CACNA2D4</i> gene encoding cause heterogeneous forms vision impairment underlying pathogenic mechanisms which remain unclear. To investigate retinal α<sub>2</sub>δ-4, we used genome editing to generate knock-out (α<sub>2</sub>δ-4 KO) mouse. male female KO mice, rod spherules lack...
Globally inhibiting CaM kinase activity in Drosophila, using a variety of genetic techniques, disrupts associative memory yet leaves visual and chemosensory perception intact. These studies implicate the plastic processes underlying learning but do not identify neural circuitry that specifies behavior. In this study, we use GAL4/UAS binary expression system to define areas brain require for modulation courtship conditioning. The kinase-dependent neurons determine response mated female during...
Rationale: The sodium–calcium exchanger 1 (NCX1) is predominantly expressed in the heart and implicated controlling automaticity isolated sinoatrial node (SAN) pacemaker cells, but potential role of NCX1 determining rate vivo unknown. Objective: To determine Ncx1 rate. Methods Results: We used global myocardial SAN-targeted conditional knockout ( −/− ) mice to measure effect NCX current on pacemaking activity vivo, ex SAN cells. induced using a Cre/loxP system. Unexpectedly, hearts cells...
In Drosophila, calcium/calmodulin-dependent protein kinase II (CaM kinase) has been shown to be important in the expression of both learning and memory for associative behavior courtship conditioning. this study we examine role visual input producing effects modifying on CaM kinase-dependent formation. Inhibition blocked apparent regardless input. Visual selectively affected phase conditioning: normal masked inhibition resulting generation without learning, whereas disruption revealed...
The multifunctional Ca 2+ /calmodulin-dependent kinase II (CaMKII) is activated by vasoconstrictors in vascular smooth muscle cells (VSMC), but its impact on vasoconstriction remains unknown. We hypothesized that CaMKII inhibition VSMC decreases vasoconstriction. Using novel transgenic mice express the inhibitor peptide CaMKIIN (TG SM-CaMKIIN), we investigated effect of L-type channel current ( I ), cytoplasmic and sarcoplasmic reticulum , mesenteric arteries. In VSMC, significantly reduced...
Background— Catecholamines increase heart rate by augmenting the cAMP-responsive hyperpolarization-activated cyclic nucleotide-gated channel 4 pacemaker current ( I f ) and promoting inward Na + /Ca 2+ exchanger NCX a “Ca clock” mechanism in sinoatrial nodal cells (SANCs). The importance, identity, function of signals that connect Ca clock mechanisms are uncertain controversial, but multifunctional /calmodulin-dependent protein kinase II (CaMKII) is required for physiological responses to...
Courtship and courtship conditioning are behaviors that regulated by multiple sensory inputs, including chemosensation vision. Globally inhibiting CaMKII activity in Drosophila disrupts plasticity while leaving visual chemosensory perception intact. Light has been shown to modulate CaMKII-dependent memory formation this paradigm the circuitry for nonvisual version of behavior investigated. In paradigm, volatile tactile pheromones provide primary driving force courtship, is dependent upon...
The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is a crucial mediator of cardiac physiology pathology. Increased expression activation CaMKII has been linked to elevated risk for arrhythmic events hallmark human heart failure. A useful approach determining CaMKII's role therein large-scale analysis phosphorylation by mass spectrometry. However, current phosphoproteomics approaches have proved inadequate high-fidelity identification kinase-specific roles....