A5041806359- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Metabolism and Genetic Disorders
- Peroxisome Proliferator-Activated Receptors
- Hemoglobin structure and function
- Acute Kidney Injury Research
- Diet and metabolism studies
- Eicosanoids and Hypertension Pharmacology
- Fungal and yeast genetics research
- Metabolism, Diabetes, and Cancer
- Electron Spin Resonance Studies
- Alcohol Consumption and Health Effects
- Neurological and metabolic disorders
- Plant Gene Expression Analysis
- Teratomas and Epidermoid Cysts
- Chemotherapy-induced organ toxicity mitigation
- Cancer, Lipids, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Metabolomics and Mass Spectrometry Studies
- Fetal and Pediatric Neurological Disorders
- Sphingolipid Metabolism and Signaling
- Carcinogens and Genotoxicity Assessment
- Advanced Glycation End Products research
- Mitochondrial Function and Pathology
- Glycosylation and Glycoproteins Research
University of Pittsburgh
2014-2025
Pittsburg State University
2024
Children's Hospital of Pittsburgh
2023
University of Pittsburgh Medical Center
2023
University of Maryland, Baltimore
2012
Dicarboxylic fatty acids are generated in the liver and kidney a minor pathway called acid ω-oxidation. The effects of consuming dicarboxylic as an alternative source dietary fat have not been explored. Here, we fed dodecanedioic acid, 12-carbon (DC12), to mice at 20% daily caloric intake for nine weeks. DC12 increased metabolic rate, reduced body fat, improved glucose tolerance. We observed DC12-specific breakdown products liver, kidney, muscle, heart, brain, indicating that oral escaped...
The glucose analog 2-deoxyglucose (2DG) inhibits the growth of Saccharomyces cerevisiae and human tumor cells, but its modes action have not been fully elucidated. Yeast cells lacking Snf1 (AMP-activated protein kinase) are hypersensitive to 2DG. Overexpression either two low-affinity, high-capacity transporters, Hxt1 Hxt3, suppresses 2DG hypersensitivity snf1Δ cells. addition or loss reduces HXT1 HXT3 expression levels stimulates transporter endocytosis degradation in vacuole....
The renal tubular epithelial cells (RTECs) are particularly vulnerable to acute kidney injury (AKI). While fatty acids the preferred energy source for RTECs via acid oxidation (FAO), FAO-mediated H2O2 production in mitochondria has been shown be a major of oxidative stress. We have previously that mitochondrial flavoprotein, long-chain acyl-CoA dehydrogenase (LCAD), which catalyzes key step FAO, directly produces vitro. Further, we showed LCAD becomes hyposuccinylated during AKI. Here,...
Abstract Aerobic glycolysis is a metabolic pathway utilized by human cancer cells and also yeast when they ferment glucose to ethanol. Both are inhibited the presence of low concentrations 2-deoxyglucose (2DG). Genetic screens in used resistance identify small set genes that function regulating metabolism. A recent high throughput screen for identified much larger seemingly unrelated genes. Here, we demonstrate these newly do not fact confer significant 2-deoxyglucose. Further, show relative...
Significance Statement In this study, we demonstrate that a common, low-cost compound known as octanedioic acid (DC 8 ) can protect mice from kidney damage typically caused by ischemia-reperfusion injury or the chemotherapy drug cisplatin. This seems to enhance peroxisomal activity, which is responsible for breaking down fats, without adversely affecting mitochondrial function. DC not only affordable and easy administer but also effective. These encouraging findings suggest could potentially...
Succinylation is an understudied posttranslational modification that has been shown to increase peroxisomal activity. Furthermore, increased activity reduce oxidative stress and protect proximal tubules after acute kidney injury. Analysis of mass spectrometry succinylomic proteomic data reveals a novel role for Parkinson’s related Park7 in mediating Nrf2 antioxidant response This protection pathway provides new insights injury prevention development therapeutics.
Karyomegalic interstitial nephritis (KIN) is a genetic adult-onset chronic kidney disease (CKD) characterized by genomic instability and mitotic abnormalities in the tubular epithelial cells. KIN caused recessive mutations FAN1 DNA repair enzyme. However, endogenous source of damage FAN1/KIN kidneys has not been identified. Here we show, using FAN1-deficient human renal cells (hRTECs) FAN1-null mice as model KIN, that pathophysiology triggered hypersensitivity to reactive oxygen species...
Abstract The monomeric heme protein myoglobin (Mb), traditionally thought to be expressed exclusively in cardiac and skeletal muscle, is now known approximately 40% of breast tumors. While Mb expression associated with better patient prognosis, the molecular mechanisms by which limits cancer progression are unclear. In Mb’s predominant function oxygen storage delivery, dependent on protein’s moiety. However, prior studies demonstrate that low levels cells preclude this function. Recent...
Lysine succinylation, and its reversal by sirtuin-5 (SIRT5), is known to modulate mitochondrial fatty acid β-oxidation (FAO). We recently showed that feeding mice dodecanedioic acid, a 12-carbon dicarboxylic (DC12) can be chain-shortened four rounds succinyl-CoA, drives high-level protein hypersuccinylation in the peroxisome, particularly on peroxisomal FAO enzymes. However, ability of SIRT5 reverse DC12-induced or regulate this context, remained unexplored. Here, we DC12 strongly recruits...
Abstract Despite significant improvement in the treatment outcome of hormone responsive post-menopausal breast cancer, some eventually acquire resistance to AIs. Using our MCF-7Ca xenograft model, we observed that although, AI anastrozole inhibited tumor growth, tumors began grow. Our previous data shows resistant upregulate growth factor receptor pathways as they adapt grow low estrogen environment. In current study, investigated effect inhibiting with two signal transduction inhibitors. We...
ABSTRACT Proximal tubular epithelial cells (PTECs) are particularly vulnerable to acute kidney injury (AKI). While fatty acids the preferred energy source for PTECs via acid oxidation (FAO), FAO-mediated H 2 O production in mitochondria has been shown be a major of oxidative stress. We have previously that mitochondrial flavoprotein, long-chain acyl-CoA dehydrogenase (LCAD), which catalyzes key step FAO, directly produces vitro . Further we established loss lysine deacylase, Sirtuin 5 (...
Lysine succinylation, and its reversal by sirtuin-5 (SIRT5), is known to modulate mitochondrial fatty acid β-oxidation (FAO). We recently showed that feeding mice dodecanedioic acid, a 12-carbon dicarboxylic (DC12) can be chain-shortened four rounds succinyl-CoA, drives high-level protein hypersuccinylation in the peroxisome, particularly on peroxisomal FAO enzymes. But ability of SIRT5 reverse DC12-induced or regulate this context, remained unexplored. Here, we DC12 strongly recruits into...
Introduction Lysine succinylation is a post-translational modification associated with the control of several diseases, including acute kidney injury (AKI). It suggested that hypersuccinylation favors peroxisomal fatty acid oxidation (FAO) instead mitochondrial. In addition, medium-chain acids (MCFAs) dodecanedioic (DC 12 ) and octanedioic 8 ), upon FAO, generate succinyl-CoA, resulting in hypersuccinylation. DC convenient, inexpensive, easily administered, efficient. We believe this study...