Mary McCoy

University of California, Merced

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i-10 index

Research Field

Deletion of murine Arv1 results in a lean phenotype with increased energy expenditure

Nutrition and Diabetes (2015)

William R. Lagor Fumin Tong Kelsey E. Jarrett Wen Lin Donna Conlon

Abstract Background: ACAT-related enzyme 2 required for viability 1 ( ARV1 ) is a putative lipid transporter of the endoplasmic reticulum that is conserved across eukaryotic species. The ARV1 protein contains a conserved N-terminal cytosolic zinc ribbon motif known as the ARV1 homology domain, followed by multiple transmembrane regions anchoring it in the ER. Deletion of ARV1 in yeast results in defective sterol trafficking, aberrant lipid synthesis, ER stress, membrane disorganization and hypersensitivity to fatty acids (FAs). We sought to investigate the role of Arv1 in mammalian lipid metabolism. Methods: Homologous recombination was used to disrupt the Arv1 gene in mice. Animals were examined for alterations in lipid and lipoprotein levels, body weight, body composition, glucose tolerance and energy expenditure. Results: Global loss of Arv1 significantly decreased total cholesterol and high-density lipoprotein cholesterol levels in the plasma. Arv1 knockout mice exhibited a dramatic lean phenotype, with major reductions in white adipose tissue (WAT) mass and body weight on a chow diet. This loss of WAT is accompanied by improved glucose tolerance, higher adiponectin levels, increased energy expenditure and greater rates of whole-body FA oxidation. Conclusions: This work identifies Arv1 as an important player in mammalian lipid metabolism and whole-body energy homeostasis.

Lipid droplet

10.1038/nutd.2015.32

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Citations (16)

Endothelial Lipase Activity Predicts High-Density Lipoprotein Catabolism in Hemodialysis

Arteriosclerosis Thrombosis and Vascular Biology (2012)

Verónica Miksztowicz Mary McCoy Laura Schreier Leonardo Cacciagiú Alicia Elbert

A novel phospholipase assay was used to measure for the first time the behavior of endothelial and hepatic phospholipase activities in postheparin human plasma of hemodialyzed patients and its relationship with atherogenic and antiatherogenic lipoprotein levels.Endothelial and hepatic phospholipase activity was assessed in a total SN1-specific phospholipase assay, using (1-decanoylthio-1-deoxy-2-decanoyl-sn-glycero-3-phosphoryl) ethylene glycol as the substrate. Hemodialyzed patients presented lower values of total and hepatic phospholipase activity than controls: 4.4 (1.9-9.0) versus 7.5 (3.6-18.0) and 2.6 (0.7-6.2) versus 6.6 (1.3-15.2) μmol of fatty acid released per milliliter of postheparin plasma per hour, respectively (P<0.001); however, endothelial lipase (EL) phospholipase activity was increased in patients: 1.7 (0.8-3.0) versus 1.1 (0.1-2.7) μmol of fatty acid released per milliliter of postheparin plasma per hour (P=0.008). EL was negatively associated with high-density lipoprotein (HDL)-cholesterol (r=-0.427; P=0.001), and apolipoprotein A-I levels, total phospholipase, and hepatic lipase activity were directly associated with low-density lipoprotein-cholesterol and apolipoprotein B. The association of EL and HDL-cholesterol remained significant when adjusting for waist circumference (β=-0.26; P=0.05), and the effect of hepatic lipase on low-density lipoprotein-cholesterol continued after adjusting for age (β=0.46; P= 0.001).Our results support the hypothesis that EL is the predominant enzyme responsible for lipolytic catabolism of HDLs in hemodialyzed patients and resolve the apparent paradox observed between low hepatic lipase activity and decreased HDL-cholesterol levels observed in these patients. In addition, the ability to assess total hepatic lipase and EL phospholipase activity in plasma will increase our knowledge of the mechanisms involved in controlling HDL levels and cardiovascular risk in hemodialyzed patients, as well as other populations with low levels of HDL-cholesterol.

Catabolism

10.1161/atvbaha.112.300110

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Citations (14)

Potent and Selective PPAR-α Agonist LY518674 Upregulates Both ApoA-I Production and Catabolism in Human Subjects With the Metabolic Syndrome

Arteriosclerosis Thrombosis and Vascular Biology (2008)

John S. Millar Danielle Duffy Ramprasad Gadi LeAnne T. Bloedon Richard L. Dunbar

Objective— The study of PPAR-α activation on apoA-I production in humans has been limited to fibrates, relatively weak PPAR-α agonists that may have other molecular effects. We sought to determine the effect of a potent and highly specific PPAR-α agonist, LY518674, on apoA-I, apoA-II, and apoB-100 kinetics in humans with metabolic syndrome and low levels of HDL cholesterol (C). Methods and Results— Subjects were randomized to receive LY518674 (100 μg) once daily (n=13) or placebo (n=15) for 8 weeks. Subjects underwent a kinetic study using a deuterated leucine tracer to measure apolipoprotein production and fractional catabolic rates (FCR) at baseline and after treatment. LY518674 significantly reduced VLDL-C (−38%, P =0.002) and triglyceride (−23%, P =0.002) levels whereas LDL-C and HDL-C levels were unchanged. LY518674 significantly reduced VLDL apoB-100 (−12%, P =0.01) levels, attributable to an increased VLDL apoB-100 FCR with no change in VLDL apoB-100 production. IDL and LDL apoB-100 kinetics were unchanged. LY518674 significantly increased the apoA-I production rate by 31% ( P <0.0001), but this was accompanied by a 33% increase in the apoA-I FCR ( P =0.002), resulting in no change in plasma apoA-I. There was a 71% increase in the apoA-II production rate ( P <0.0001) accompanied by a 25% increase in the FCR ( P <0.0001), resulting in a significant increase in plasma apoA-II. Conclusions— Activation of PPAR-α with LY518674 (100 μg) in subjects with metabolic syndrome and low HDL-C increased the VLDL apoB-100 FCR consistent with enhanced lipolysis of plasma triglyceride. Significant increases in the apoA-I and apoA-II production rates were accompanied by increased FCRs resulting in no change in HDL-C levels. These data indicate a major effect of LY518674 on the production and clearance of apoA-I and HDL despite no change in the plasma concentration. The effect of these changes on reverse cholesterol transport remains to be determined.

Catabolism

10.1161/atvbaha.108.171223

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Citations (41)

LEA_4 motifs function alone and in conjunction with synergistic cosolutes to protect a labile enzyme during desiccation

bioRxiv (Cold Spring Harbor Laboratory) (2024)

Vincent Nicholson Kenny Nguyen Edith Gollub Mary McCoy Feng Yu

Organisms from all kingdoms of life depend on Late Embryogenesis Abundant (LEA) proteins to survive desiccation. LEA proteins are divided into broad families distinguished by the presence of family-specific motif sequences. The LEA_4 family, characterized by eleven-residue motifs, plays a crucial role in the desiccation tolerance of numerous species. However, the role of these motifs in the function of LEA_4 proteins is unclear, with some studies finding that they recapitulate the function of full-length LEA_4 proteins in vivo, and other studies finding the opposite result. In this study, we characterize the ability of LEA_4 motifs to protect a desiccation-sensitive enzyme, citrate synthase, from loss of function during desiccation. We show here that LEA_4 motifs not only prevent the loss of function of citrate synthase during desiccation, but also that they can do so more robustly via synergistically interactions with cosolutes. Our analysis further suggests that cosolutes induce synergy with LEA_4 motifs in a manner that correlates with transfer free energy (TFE). This research advances our understanding of LEA_4 proteins by demonstrating that during desiccation their motifs can protect specific clients to varying degrees and that their protective capacity is modulated by their chemical environment. Our findings extend beyond the realm of desiccation tolerance, offering insights into the interplay between IDPs and cosolutes. By investigating the function of LEA_4 motifs, we highlight broader strategies for understanding protein stability and function.

Conjunction (astronomy)

10.1101/2024.09.04.611296

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Citations (0)

Determining hepatic triglyceride production in mice: comparison of poloxamer 407 with Triton WR-1339

Journal of Lipid Research (2005)

John S. Millar Debra Cromley Mary McCoy Daniel J. Rader Jeffrey T. Billheimer

10.1194/jlr.d500019-jlr200

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Citations (251)

5'-nucleotide phosphodiesterase isoenzyme in patients with hepatitis B infection.

PubMed (1975)

K. C. Tsou Mary McCoy K.W. Lo W. T. London

The hypothesis that hepatitis B infection is etiologically related to hepatoma has been investigated by studying the interrelationships between hepatitis B surface antigen (HBsAg, Australia antigen) and the fast-moving 5'-nucleotide phosphodiesterase Band V isoenzyme (5'-NPDase-V). Sera from 58 patients with viral hepatitis were tested for 5'-NPDase-V and HBsAg. The isoenzyme was found in 34 of 37 patients who were also positive for HBsAg but in only 4 of 21 hepatitis patients who were HBsAg negative. Five patients convalescing from hepatitis were negative for both HBsAg and the isoenzyme. Preparative gel electrophoresis showed that these 2 markers were different proteins. Of 34 hepatoma patients, 29 were positive for 5'-NPDase-V. Only 1 isoenzyme-positive patient was positive for HBsAg by counterimmunoelectrophoresis. However, of 16 isoenzyme-positive hepatoma patients available for radioimmunoassay, 8 were NBsAg positive (50%). None of 21 hepatoma samples tested for antibody to NBsAg was positive. Of 21 "normal" carriers of HBsAg and 10 carriers with Down's syndrome, 4 persons were detected with the isoenzyme. The results suggest that HBsAg and 5'-NPDase-V in the presence of liver damage are associated and thus provide a new marker enzyme between hepatitis B infection and hepatoma.

Counterimmunoelectrophoresis

Hepatitis B

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Citations (3)

High-Density Lipoprotein (HDL) Phospholipid Content and Cholesterol Efflux Capacity Are Reduced in Patients With Very High HDL Cholesterol and Coronary Disease

Arteriosclerosis Thrombosis and Vascular Biology (2015)

Anandita Agarwala Amrith Rodrigues Marjorie Risman Mary McCoy Kevin Trindade

Objective— Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD), and high HDL-C is generally associated with reduced risk of CAD. Extremely high HDL-C with CAD is an unusual phenotype, and we hypothesized that the HDL in such individuals may have an altered composition and reduced function when compared with controls with similarly high HDL-C and no CAD. Approach and Results— Fifty-five subjects with very high HDL-C (mean, 86 mg/dL) and onset of CAD at the age of ≈60 years with no known risk factors for CAD (cases) were identified through systematic recruitment. A total of 120 control subjects without CAD, matched for race, sex, and HDL-C level (controls), were identified. In all subjects, HDL composition was analyzed and HDL cholesterol efflux capacity was assessed. HDL phospholipid composition was significantly lower in cases (92±37 mg/dL) than in controls (109±43 mg/dL; P =0.0095). HDL cholesterol efflux capacity was significantly lower in cases (1.96±0.39) than in controls (2.11±0.43; P =0.04). Conclusions— In people with very high HDL-C, reduced HDL phospholipid content and cholesterol efflux capacity are associated with the paradoxical development of CAD.

High-density lipoprotein

Efflux

Reverse cholesterol transport

10.1161/atvbaha.115.305504

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Citations (95)

5'-Nucleotide phosphodiesterase isoenzyme pattern in the serum of human hepatoma.

PubMed (1973)

K. C. Tsou S. L. Ledis Mary McCoy

Summary The isoenzyme patterns for 5′-nucleotide phosphodiesterase in human sera have been studied by the use of a 5′-(5-iodoindoxyl) nucleoside phosphodiester as a histochemical substrate after electrophoresis on polyacrylamide gel support. Normal sera show two major, fast-moving bands and two weak, slow-moving bands. All six sera from patients having histologically identified primary hepatoma show an additional, fast-moving isoenzyme band compared to normal serum, and a benign liver adenoma serum shows no such additional isoenzyme band. Furthermore, this last, fast-moving isoenzyme is not seen in neonatal serum. Since these six cases of hepatoma sera are all negative with anti-α-fetoprotein serum by the double immunodiffusion test, the presence of this isoenzyme in these sera could be an alternate diagnostic aid.

Ouchterlony double immunodiffusion

Immunodiffusion

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Citations (32)

701: THE ASSOCIATION BETWEEN EEG ABNORMALITIES ON RAPID RESPONSE EEG AND OUTCOME IN SEPTIC PATIENTS

Critical Care Medicine (2025)

Zed Seedat Walter Mickey Gustavo Padron Alina Khan Mary McCoy

Association (psychology)

10.1097/01.ccm.0001101468.92064.ad

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592: RAPID-RESPONSE EEG IN ICU: ENHANCING NEUROLOGIC MONITORING AND MANAGEMENT

Critical Care Medicine (2023)

Zed Seedat Jideofor Obodozie Alina Khan Gustavo Padron Kimberly Fowler

Introduction: The timely diagnosis and treatment of patients with seizures can prevent significant morbidity and mortality. During off-hours, treatment decisions are made on the basis of clinical suspicion alone, which results in the potential for missing non-convulsive seizures (NCS) and overtreating of patients without seizure. Advancements in rapid response EEG (rEEG, Ceribell Inc) has enabled continuous monitoring and trend analysis of cerebral electrical activity that aids in the early detection of NCS and epileptiform patterns (EP), like lateralized periodic discharges (LPD), generalized periodic discharges (GPD), and triphasic waves (TP). Methods: A total of 428 ICU patients underwent evaluation of possible seizures with rEEG between 09/2020 – 05/2023). Automated detection of seizure burden throughout a recording (calculated as the percentage of ten-second epochs with seizure activity in any 5-min EEG segment) was performed with Claritγ (≥ 90% indicating ≥ 4.5 min of seizure activity and triggering a status epilepticus alert which prompts treatment, 10 - 90 % burden prompts call to epileptologist, and < 10 % indicates absence of NCS or EP and thus no calls or treatments necessary). ALL EEGs were reviewed by epileptologist. Results: A total of 428 rEEGs were performed during after-hours for an average duration of 9.5 +/- 0.3 hours on patients with average age (60 +/- 17 years), gender (54 % male), APACHE III scores (57 +/- 28), acute physiologic scores (46 +/- 26), and reason for EEG (unexplained encephalopathy in 64 %, seizure-like activity in 55 %, automatisms in 28 %, convulsive seizures in 8%, and post-cardiac arrest in 10%). NCS (> 90%) was detected in 24 patients (5.6 %), 10 -90 % in 146 (34 %) [Epileptologist read: Seizure in 4.8 %, LPD in 2.7 %, and TP in 1.4 %], and no seizures (0 -10 %) in 258 (60.4 %). rEEG was replaced by conventional EEG in 265 (62 %) with following: NCS in 3.6 %, LPD in 7.2 %, GPD in 10 %, and TP in 10 %. Conclusions: rEEG is useful in diagnosis and treatment of patients with nonconvulsive seizures and in preventing undertreatment or overtreatment of seizures. By enabling timely detection and intervention, it has the potential to improve patient outcomes and reduce morbidity. Further research is needed to fully establish the utility of rapid response EEG in the ICU.

10.1097/01.ccm.0001000544.63264.d3

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