A5021799554- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Metabolism and Genetic Disorders
- RNA Research and Splicing
- Genetics, Aging, and Longevity in Model Organisms
- Pancreatic function and diabetes
- Wnt/β-catenin signaling in development and cancer
- Polyamine Metabolism and Applications
- Neuroscience and Neuropharmacology Research
- Neurogenetic and Muscular Disorders Research
- Amino Acid Enzymes and Metabolism
- RNA modifications and cancer
- Mast cells and histamine
- Cancer, Hypoxia, and Metabolism
- Muscle metabolism and nutrition
- Amyotrophic Lateral Sclerosis Research
- Neurotransmitter Receptor Influence on Behavior
- Sulfur Compounds in Biology
- Spinal Cord Injury Research
- Cancer-related gene regulation
- Endoplasmic Reticulum Stress and Disease
- Health, Environment, Cognitive Aging
- Memory and Neural Mechanisms
The University of Texas Southwestern Medical Center
2023-2024
Southwestern Medical Center
2024
Oklahoma Medical Research Foundation
2015-2023
The University of Texas Health Science Center at San Antonio
2006-2015
Oklahoma City VA Medical Center
2015
South Texas Veterans Health Care System
2011
The University of Texas Health Science Center at Houston
2008
Summary Sarcopenia, the loss of skeletal muscle mass and function during aging, is a major contributor to disability frailty in elderly. Previous studies found protective effect reduced histone deacetylase activity models neurogenic atrophy. Because aging associated with motor neuron innervation, we investigated potential for ( HDAC ) inhibitor butyrate modulate age‐related loss. Consistent previous studies, significant hindlimb 26‐month‐old C57Bl/6 female mice fed control diet. Butyrate...
We tested the hypothesis that AMP-activated protein kinase (AMPK), an energy sensor, regulates diabetes-induced renal hypertrophy. In kidney glomerular epithelial cells, high glucose (30 mM), but not equimolar mannitol, stimulated de novo synthesis and induced hypertrophy in association with increased phosphorylation of eukaryotic initiation factor 4E binding 1 decreased elongation 2, regulatory events mRNA translation. These high-glucose-induced changes were phosphatidylinositol 3-kinase,...
Hydrogen sulfide, a signaling gas, affects several cell functions. We hypothesized that hydrogen sulfide modulates high glucose (30 mm) stimulation of matrix protein synthesis in glomerular epithelial cells. High global synthesis, cellular hypertrophy, and laminin type IV collagen content was inhibited by sodium hydrosulfide (NaHS), an H(2)S donor. activation mammalian target rapamycin (mTOR) complex 1 (mTORC1), shown phosphorylation p70S6 kinase 4E-BP1, NaHS. stimulated mTORC1 to promote...
Abstract Background Cancer cachexia occurs in approximately 80% of cancer patients and is a key contributor to cancer‐related death. The mechanisms controlling development tumour‐induced muscle wasting are not fully elucidated. Specifically, the progression underexplored. Therefore, we examined skeletal protein turnover throughout tumour‐bearing mice. Methods Lewis lung carcinoma (LLC) was injected into hind flank C57BL6/J mice at 8 weeks age with tumour allowed develop for 1, 2, 3, or 4...
Molecular targets to reduce muscle weakness and atrophy due oxidative stress have been elusive. Here we show that activation of Sarcoplasmic Reticulum (SR) Ca2+ ATPase (SERCA) with CDN1163, a novel small molecule allosteric SERCA activator, ameliorates the impairment in CuZnSOD deficient (Sod1-/-) mouse model stress. Sod1-/- mice are characterized by reduced activity, atrophy, increased mitochondrial dysfunction. Seven weeks CDN1163 treatment completely restored activity reversed 23%...
Many Amyotrophic Lateral Sclerosis (ALS) patients experience hypermetabolism, or an increase in measured versus calculated metabolic rate. The cause of hypermetabolism and the effects on neuronal metabolism ALS are currently unknown, but efficacy dietary interventions shows promise for as therapeutic target. goal this study is to measure changes pathways a function disease progression spinal cords SOD1G93A mouse model ALS. We conducted comprehensive assessment protein expression pathways,...
Our previous studies showed that adult (8 month) mice lacking CuZn-superoxide dismutase (CuZnSOD, Sod1KO mice) have neuromuscular changes resulting in dramatic accelerated muscle atrophy and weakness mimics age-related sarcopenia. We further shown loss of CuZnSOD targeted to skeletal alone results only mild no atrophy. In this study, we deletion specifically neurons (nSod1KO determined the effect on mass weakness. The nSod1KO show a significant activity protein level brain spinal cord but...
We examined the effect of rapamycin on life span a mouse model type 2 diabetes, db/db mice. At 4 months age, male and female C57BLKSJ- leprdb/db mice ( ) were placed either control diet, lacking or diet containing maintained these diets over their span. Rapamycin was found to reduce The median survival fed 349 302 days, respectively, 487 411 respectively. Adjusting for gender differences, increased mortality risk 1.7-fold in both End-of-life pathological data showed that suppurative...
High glucose (30 mM) and high insulin (1 nM), pathogenic factors of type 2 diabetes, increased mRNA expression synthesis lamininbeta1 fibronectin after 24 h incubation in kidney proximal tubular epithelial (MCT) cells. We tested the hypothesis that inactivation glycogen synthase kinase 3beta (GSK3beta) by induces increase laminin beta1 via activation eIF2Bepsilon. Both induced Ser-9 phosphorylation GSK3beta at lasted for up to 48 h. This was associated with dephosphorylation eIF2Bepsilon...
We explored molecular events associated with aging-induced matrix changes in the kidney. C57BL6 mice were studied youth, middle age, and old age. Albuminuria serum cystatin C level (an index of glomerular filtration) increased aging. Renal hypertrophy was evident middle-aged glomerulomegaly increase mesangial fraction occupied by extracellular matrix. Content collagen types I III fibronectin aging; increment their mRNA varied phase The content ZEB1 ZEB2, type transcription inhibitors,...
Increase in protein synthesis contributes to kidney hypertrophy and matrix accumulation diabetes. We have previously shown that high glucose-induced is associated with inactivation of glycogen synthase kinase 3β (GSK3β) renal cells the kidneys diabetic mice. tested whether activation GSK3β by sodium nitroprusside (SNP) mitigates injury Studies kidney-proximal tubular epithelial showed SNP abrogated laminin increment stimulating inhibiting Akt, mTORC1, events mRNA translation regulated mTORC1...
Diabetes-induced kidney cell injury involves an increase in matrix protein expression that is only partly alleviated by current treatment, prompting a search for new modalities. We have previously shown hydrogen sulfide (H2S) inhibits high glucose-induced synthesis podocytes. tested whether tadalafil, phosphodiesterase 5 inhibitor used to treat erectile dysfunction, ameliorates glucose stimulation of proteins generating H2S Tadalafil abrogated global and laminin γ1. inhibited activation...
Abstract Defects in neuromuscular innervation contribute significantly to the age-related decline muscle mass and function (sarcopenia). Our previous studies demonstrated that denervation induces mitochondrial hydroperoxide production (H 2 O lipid hydroperoxides (LOOHs)). Here we define relative contribution of electron transport chain (ETC) derived H versus cytosolic phospholipase A (cPLA ) LOOHs neurogenic atrophy. We show increases cPLA protein content, activity, metabolites downstream...
Diabetes promotes protein synthesis to induce kidney hypertrophy and increase renal matrix proteins. Increased capacity for mRNA translation by way of ribosomal biogenesis facilitates sustained stimulation synthesis. We tested the hypothesis that high glucose induces as indicated an in rRNA setting augmented High (30 mM) increased global synthesis, expression proteins, laminin γ1 fibronectin, rDNA transcription glomerular epithelial cells (GECs) compared with 5 mM glucose. induced Ser388...
Mitochondria are established essential regulators of cellular function and metabolism. regulate redox homeostasis, maintain energy (ATP) production through oxidative phosphorylation, buffer calcium levels control cell death apoptosis. In addition to these critical functions, recent evidence supports a signaling role for mitochondria. For example, studies over the past few years have that peptides released from mitochondria mediate stress responses such as mitochondrial unfolded protein...
Mice deficient in the electron transport chain (ETC) complex IV assembly protein SURF1 have reduced and activity of cytochrome c oxidase that is associated with an upregulation components mitochondrial unfolded response (UPRMT) increased number. We hypothesized proteins UPRMT to Surf1−/− mice might contribute stress resistance. To test this hypothesis we asked whether primary cultures fibroblasts from exhibit enhanced resistance stressors compared wild-type fibroblasts. Here show dermal...