Digital Commons Network^™

Radiation-Induced Glutamate Transport Alterations In Neuron-Astrocyte Coupling, Martha Celia Sanchez

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure of the central nervous system (CNS) to ionizing radiation is known to result in behavioral, cognitive, and motor deficits - effects similar to those seen in many neurodegenerative disorders. Neurons and astrocytes, two principal cell types in the brain, coexist as an interdependent metabolic unit via the neurotransmitter glutamate. Disruption of this metabolic coupling would have widespread effects within the CNS, therefore it is hypothesized that ionizing radiation impairs glutamate transport and metabolism, and increases oxidative stress, ultimately impairing neuron-astrocyte coupling. We propose to investigate the mechanism and determine the impetus for radiation-induced neurotoxicity by measuring the temporal sequence …

Incorporating Ethnicity Into Genetic Risk Assessment For Alzheimer Disease: The Reveal Study Experience, Peter J. Whitehouse, Melissa Barber Butson

Faculty Scholarship

PURPOSE: To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants. METHODS: The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicity-specific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease. RESULTS: Review of epidemiological data suggested notable differences in risk between African …

Functional Interactions Of Alcohol-Sensitive Sites In The N-Methyl-D-Aspartate Receptor M3 And M4 Domains, Hong Ren, Abdelghaffar K. Salous, Jaclyn M. Paul, Kaitlin A. Lamb, Donard S. Dwyer, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

The N-methyl-d-aspartate receptor is an important mediator of the behavioral effects of ethanol in the central nervous system. Previous studies have demonstrated sites in the third and fourth membrane-associated (M) domains of the N-methyl-d-aspartate receptor NR2A subunit that influence alcohol sensitivity and ion channel gating. We investigated whether two of these sites, Phe-637 in M3 and Met-823 in M4, interactively regulate the ethanol sensitivity of the receptor by testing dual substitution mutants at these positions. A majority of the mutations decreased steady-state glutamate EC₅₀ values and maximal steady-state to peak current ratios (I_ss/I …

Gating Charge Immobilization In Kv4.2 Channels: The Basis Of Closed-State Inactivation., Kevin Dougherty, Jose A De Santiago-Castillo, Manuel Covarrubias

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Kv4 channels mediate the somatodendritic A-type K+ current (I(SA)) in neurons. The availability of functional Kv4 channels is dynamically regulated by the membrane potential such that subthreshold depolarizations render Kv4 channels unavailable. The underlying process involves inactivation from closed states along the main activation pathway. Although classical inactivation mechanisms such as N- and P/C-type inactivation have been excluded, a clear understanding of closed-state inactivation in Kv4 channels has remained elusive. This is in part due to the lack of crucial information about the interactions between gating charge (Q) movement, activation, and inactivation. To overcome this limitation, we engineered a charybdotoxin …

Application Of Prodrugs To Inflammatory Diseases Of The Gut, Helieh S. Oz, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Oral delivery is the most common and preferred route of drug administration although the digestive tract exhibits several obstacles to drug delivery including motility and intraluminal pH profiles. The gut milieu represents the largest mucosal surface exposed to microorganisms with 10^10-12 colony forming bacteria/g of colonic content. Approximately, one third of fecal dry matter is made of bacteria/ bacterial components. Indeed, the normal gut microbiota is responsible for healthy digestion of dietary fibers (polysaccharides) and fermentation of short chain fatty acids such as acetate and butyrate that provide carbon sources (fuel) for these bacteria. Inflammatory bowel disease (IBD) results …

Method For Treating A Viral Infection Related Or A Chemical Toxin Related Hepatic Injury With Deltorphin D, Peter R. Oeltgen, Paul D. Bishop, Craig J. Mcclain, Shirish Barve

Pathology and Laboratory Medicine Faculty Patents

A method of modulating cytokine mediated hepatic injury by administering compound-D SEQ ID NO:1 to a mammal. A concentration of the compound in the range of about 0.5 mg/kg to about 20 mg/kg in a physiologically acceptable formulation blocks a cytokine cascade. A therapeutic method of modulating cytokine mediated acute inflammatory, trauma induced and toxin induced hepatic injury, particularly via tumor necrosis factor modulation, is thus disclosed.

Screening Assay For Enzymes Involved In Pathophysiology Using Seldi-Tof Mass Spectrometr, Khalid M. Elased, Mariana Morris

Pharmacology and Toxicology Faculty Publications

The invention provides methods for quantifying enzymatic activity of an enzyme with a known substrate. The methods employ SELDI-TOF mass spectrometry, and are suitable, in particular, for assaying aspects of the renin-angiotensin system. The methods may be utilized to assess and/or monitor biological conditions associated with the renin-angiotensin system prior to the manifestation of known physiological and biomarkers for such conditions. The methods are suitable for analysis of pharmacological effectors of the renin-angiotensin system, and are particularly suitable for automation and high-throughput screening assay design.

Primers And Probe To Identify Mycobacterium Tuberculosis Complex, Subodh M. Lele, Manjiri S. Lele, Nada H. Khattar

Pathology and Laboratory Medicine Faculty Patents

Methods and nucleic acids for rapid, reliable and sensitive detection of Mycobacterium tuberculosis (MTB) complex pathogen in a biological sample. Oligonucleotides are provided which amplify MTB DNA and which are useful in carrying out real time PCR of DNA obtained from formalin-fixed and paraffin-embedded tissue samples.

Retinoic Acid Decreases Atf-2 Phosphorylation And Sensitizes Melanoma Cells To Taxol-Mediated Growth Inhibition, Ying Huang, Jennifer Minigh, Sarah Miles, Richard N. Niles

Biochemistry and Microbiology

Cutaneous melanoma is often resistant to chemo- and radiotherapy. This resistance has recently been demonstrated to be due, at least in part, to high activating transcription factor 2 (ATF-2) activity in these tumors. In concordance with these reports, we found that B16 mouse melanoma cells had higher levels of ATF-2 than immortalized, but non-malignant mouse melanocytes. In addition, the melanoma cells had a much higher amount of phosphorylated (active) ATF-2 than the immortalized melanocytes. In the course of determining how retinoic acid (RA) stimulates activating protein-1 (AP-1) activity in B16 melanoma, we discovered that this retinoid decreased the phosphorylation of …

Novel Role Of Antioxidant-1 (Atox1) As A Copper-Dependent Transcription Factor Involved In Cell Proliferation, S. Itoh, H. W. Kim, O. Nakagawa, K. Ozumi, Susan M. Lessner, H. Aoki, K. Akram, R. D. Mckinney, M. Ushio-Fukai, T. Fukai

Faculty Publications

Copper plays a fundamental role in regulating cell growth. Many types of human cancer tissues have higher copper levels than normal tissues. Copper can also induce gene expression. However, transcription factors that mediate copper-induced cell proliferation have not been identified in mammals. Here we show that antioxidant-1 (Atox1), previously appreciated as a copper chaperone, represents a novel copper-dependent transcription factor that mediates copper-induced cell proliferation. Stimulation of mouse embryonic fibroblasts (MEFs) with copper markedly increased cell proliferation, cyclin D1 expression, and entry into S phase, which were completely abolished in Atox1^-/- MEFs. Promoter analysis and EMSA revealed that copper …

Diabetes Alters Contraction-Induced Mitogen Activated Protein Kinase Activation In The Rat Soleus And Plantaris, Anjaiah Katta, Deborah L. Preston, Sunil K. Kakarla, Shinichi Asano, Sarath Meduru, Sriram P. Mupparaju, Ellie Yokochi, Kevin M. Rice, Devashish H. Desai, Eric R. Blough

MIIR Faculty Research

The prescription of anaerobic exercise has recently been advocated for the management of diabetes; however exercise-induced signaling in diabetic muscle remains largely unexplored. Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. Here, we compare the basal and the in situ contraction-induced phosphorylation of Erk1/2- p38- and Jnk-MAPK and their downstream targets (p90rsk and MAPKAP-K2) in the plantaris and soleus muscles of normal and obese (fa/fa) Zucker rats. Compared to lean animals, the time course and magnitude of Erk1/2, p90rsk and …

N-Acetyl-B-D-Glucosaminidase And Inflammatory Response After Cardiopulmonary Bypass, Perwaiz Iqbal, Hasanat M Sharif, Naseema Mehboobali, Farzana A Yousuf, Abrar H Khan, Frank W Sellke

Department of Biological & Biomedical Sciences

OBJECTIVE: To determine the changes in activity of plasma N-acetyl-beta-D-glucosaminidase, a marker for inflammation as well as renal, pulmonary and cardiac damage and proinflammatory cytokines in patients undergoing coronary artery bypass grafting and find out the relationship between their plasma levels with clinical outcome of patients.

STUDY DESIGN: Cross-sectional study.

PLACE AND DURATION OF STUDY: The Aga Khan University, Karachi, from January to June 2003.

PATIENTS AND METHODS: N-acetyl-beta-D-glucosaminidase (NAG) activity and concentrations of tumor necrosis factor-alpha of (TNFalpha), interleukin 6 (IL-6), interleukin 8 (IL8) and granulocyte-macrophage colony stimulating factor (GM-CSF) were monitored in plasma samples of 12 angina patients …

Composites Comprising Cholesterol And Carboxymethyl Cellulose, Vuk Uskoković

Pharmacy Faculty Articles and Research

Whereby cholesterol presents one of the major fatty substances in human body, carboxymethyl cellulose is a water-soluble derivative of cellulose, the most abundant dietary fiber. Whereas on one hand in vivo precipitation of cholesterol is the major cause of atherosclerosis, dietary fibers are on the other hand known for their ability to clean the fatty plaque deposited on intestinal pathways, and prevent its build-up in other critical areas within the organism. In this work, a method for the preparation of a composite material comprising cholesterol and carboxymethyl cellulose from 1-hexanol/water biphase mixtures is reported. Specificity of the interaction between the …

The Yin And Yang Of Fcγ Receptors In Itp, Steven E. Mckenzie

Department of Medicine Faculty Papers

The Fcγ receptors contribute to the susceptibility to autoimmune diseases such as ITP in several ways: (1) they modulate dendritic cell antigen processing and presentation, (2) they modulate antibody production by B cells, and (3) they participate in effector cell functions, such as phagocytosis, antibody-dependent cellular cytotoxicity, and mediator release. The key finding in recent years has been the appreciation that the activating Fcγ receptors, encoded by FCGR2A, -2C, -3A, and -3B, compete with the inhibitory Fcγ receptor, encoded by FCGR2B, to determine cellular responses to immune complexes and antibody-coated cells.

Fibulin-2 Is Dispensable For Mouse Development And Elastic Fiber Formation, Francois-Xavier Sicot, Takeshi Tsuda, Dessislava Markova, John Klement, Machiko Arita, Rui-Zhu Zhang, Te-Cheng Pan, Robert P. Mecham, David E. Birk, Mon-Li Chu

Department of Dermatology and Cutaneous Biology Faculty Papers

Fibulin-2 is an extracellular matrix protein belonging to the five-member fibulin family, of which two members have been shown to play essential roles in elastic fiber formation during development. Fibulin-2 interacts with two major constituents of elastic fibers, tropoelastin and fibrillin-1, in vitro and localizes to elastic fibers in many tissues in vivo. The protein is prominently expressed during morphogenesis of the heart and aortic arch vessels and at early stages of cartilage development. To examine its role in vivo, we generated mice that do not express the fibulin-2 gene (Fbln2) through homologous recombination of embryonic stem cells. Unexpectedly, the …

Abeta42 Mutants With Different Aggregation Profiles Induce Distinct Pathologies In Drosophila., Koichi Iijima, Hsueh-Cheng Chiang, Stephen A Hearn, Inessa Hakker, Anthony Gatt, Christopher Shenton, Linda Granger, Amy Leung, Kanae Iijima-Ando, Yi Zhong

Department of Biochemistry and Molecular Biology Faculty Papers

Aggregation of the amyloid-beta-42 (Abeta42) peptide in the brain parenchyma is a pathological hallmark of Alzheimer's disease (AD), and the prevention of Abeta aggregation has been proposed as a therapeutic intervention in AD. However, recent reports indicate that Abeta can form several different prefibrillar and fibrillar aggregates and that each aggregate may confer different pathogenic effects, suggesting that manipulation of Abeta42 aggregation may not only quantitatively but also qualitatively modify brain pathology. Here, we compare the pathogenicity of human Abeta42 mutants with differing tendencies to aggregate. We examined the aggregation-prone, EOFAD-related Arctic mutation (Abeta42Arc) and an artificial mutation (Abeta42art) that …

Trk: A Neuromodulator Of Age-Specific Behavioral And Neurochemical Responses To Cocaine In Mice., Michelle Niculescu, Shane A Perrine, Jonathan S Miller, Michelle E Ehrlich, Ellen M Unterwald

Farber Institute for Neuroscience Faculty Papers

Responses to psychostimulants vary with age, but the molecular etiologies of these differences are largely unknown. The goal of the present research was to identify age-specific behavioral and molecular adaptations to cocaine and to elucidate the mechanisms involved therein. Postweanling, periadolescent, and adult male CD-1 mice were exposed to cocaine (20 mg/kg) for 7 d. The rewarding effects of cocaine were assessed, as were the response to a Trk antagonist and the regulation of dopamine and cAMP-regulated phosphoprotein, 32 kDa (DARPP-32). Cocaine was rewarding in both periadolescent and adult mice using a conditioned place preference procedure. In contrast, postweanling mice …

The Expression Of Microrna Mir-107 Decreases Early In Alzheimer's Disease And May Accelerate Disease Progression Through Regulation Of Β-Site Amyloid Precursor Protein-Cleaving Enzyme 1, Wang-Xia Wang, Bernard W. Rajeev, Arnold J. Stromberg, Na Ren, Guiliang Tang, Qingwei Huang, Isidore Rigoutsos, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with …

Right-Handed 14-Helix In Β3-Peptides From L-Aspartic Acid Monomers, Kamaljit Kaur, Tara Sprules, Wael Soliman, Reem Beleid, Sahar Ahmed

Pharmacy Faculty Articles and Research

β-Peptides made from L-aspartic acid monomers form a new class of β³-peptides. Here we report the first three-dimensional NMR solution structure of a β³-hexapeptide (1) from L-aspartic acid monomers in 2,2,2-trifluoroethanol (TFE). We show that 1 forms a right-handed 14-helical structure in TFE. α-peptides from naturally occurring L-amino acids adopt a right-handed α-helix whereas β³-peptides formed from β³-amino acids derived from naturally occurring L-amino acids form left-handed 14-helices. The right-handed 14-helical conformation of 1 is a better mimic of α-peptide conformations. Using the NMR structure of 1 in TFE, we …

Diverse Antidepressants Increase Cdp-Diacylglycerol Production And Phosphatidylinositide Resynthesis In Depression-Relevant Regions Of The Rat Brain, Kimberly R. Tyeryar, Habiba O.U. Vongtau, Ashiwel S. Undieh

College of Pharmacy Faculty Papers

BACKGROUND: Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action. However, the diacylglycerol arm of phosphoinositide signaling cascades has not been systematically investigated, even though downstream targets of this cascade have been implicated in depression. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, we …

Genome-Wide Expression Profiling Reveals Transcriptomic Variation And Perturbed Gene Networks In Androgen-Dependent And Androgen-Independent Prostate Cancer Cells., Ajay P. Singh, Sangeeta Bafna, Kunal Chaudhary, Ganesh Venkatraman, Lynette Smith, James D. Eudy, Sonny L. Johansson, Ming-Fong Lin, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Previously, we have developed a unique in vitro LNCaP cell model, which includes androgen-dependent (LNCaP-C33), androgen-independent (LNCaP-C81) and an intermediate phenotype (LNCaP-C51) cell lines resembling the stages of prostate cancer progression to hormone independence. This model is advantageous in overcoming the heterogeneity associated with the prostate cancer up to a certain extent. We characterized and compared the gene expression profiles in LNCaP-C33 (androgen-dependent) and LNCaP-C81 (androgen-independent) cells using Affymetrix GeneChip array analyses. Multiple genes were identified exhibiting differential expression during androgen-independent progression. Among the important genes upregulated in androgen-independent cells were PCDH7, TPTE, TSPY, EPHA3, HGF, MET, EGF, TEM8, etc., …

Gene Expression Profile Of Neuronal Progenitor Cells Derived From Hescs: Activation Of Chromosome 11p15.5 And Comparison To Human Dopaminergic Neurons., William J Freed, Jia Chen, Cristina M Bäckman, Catherine M Schwartz, Tandis Vazin, Jingli Cai, Charles E Spivak, Carl R Lupica, Mahendra S Rao, Xianmin Zeng

Farber Institute for Neuroscience Faculty Papers

BACKGROUND: We initiated differentiation of human embryonic stem cells (hESCs) into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription.

METHODOLOGY: Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS). Individual genes as well as regions of the genome which were activated were determined.

PRINCIPAL FINDINGS: A number of genes known to be involved in the …

Repression Of Hla By Rot Is Dependent On Sae In Staphylococcus Aureus, Dongmei Li, Ambrose Cheung

Dartmouth Scholarship

The regulatory locus sae is a two-component system in Staphylococcus aureus that regulates many important virulence factors, including alpha-toxin (encoded by hla) at the transcriptional level. The SarA homologs Rot and SarT were previously shown to be repressors of hla in selected S. aureus backgrounds. To delineate the interaction of rot and sae and the contribution of sarT to hla expression, an assortment of rot and sae isogenic single mutants, a rot sae double mutant, and a rot sae sarT markerless triple mutant were constructed from wild-type strain COL. Using Northern blot analysis and transcriptional reporter gene green fluorescent protein, …

Morphine Exacerbates Hiv-1 Tat-Induced Cytokine Production In Astrocytes Through Convergent Effects On [Ca2+]I, Nf-Κb Trafficking And Transcription, Nazira El-Hage, Annadora J. Bruce-Keller, Tatiana Yakovleva, Igor Bazov, Georgy Bakalkin, Pamela E. Knapp, Kurt F. Hauser

Pharmacology and Toxicology Publications

Astroglia are key cellular sites where opiate drug signals converge with the proinflammatory effects of HIV-1 Tat signals to exacerbate HIV encephalitis. Despite this understanding, the molecular sites of convergence driving opiate-accelerated neuropathogenesis have not been deciphered. We therefore explored potential points of interaction between the signaling pathways initiated by HIV-1 Tat and opioids in striatal astrocytes. Profiling studies screening 152 transcription factors indicated that the nuclear factor-kappa B (NF-κB) subunit, c-Rel, was a likely candidate for Tat or Tat plus opiate-induced increases in cytokine and chemokine production by astrocytes. Pretreatment with the NF-κB inhibitor parthenolide provided evidence that Tat±morphine-induced …

Long Lasting Synchronization Of Calcium Oscillations By Cholinergic Stimulation In Isolated Pancreatic Islets, Min Zhang, Bernard Fendler, Bradford Peercy, Pranay Goel, Richard Bertram, Arthur Sherman, Leslie Satin

Pharmacology and Toxicology Publications

Abstract

Individual mouse pancreatic islets exhibit oscillations in [Ca²⁺]_i and insulin secretion in response to glucose in vitro, but how the oscillations of a million islets are coordinated within the human pancreas in vivo is unclear. Islet to islet synchronization is necessary, however, for the pancreas to produce regular pulses of insulin. To determine whether neurohormone release within the pancreas might play a role in coordinating islet activity, [Ca²⁺]_i changes in 4–6 isolated mouse islets were simultaneously monitored before and after a transient pulse of a putative synchronizing agent. The degree of synchronicity was …

Book Review: Drugs During Pregnancy And Lactation: Treatment Options And Risk Assessment, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

The Function And Mechanism Of Chmp1a In Tumor Development, Jing Li

Theses, Dissertations and Capstones

Chmp1A (Chromatin modifying protein 1A/Charged multivesicular protein 1A) is a member of the ESCRT-III (Endosomal Sorting Complex Required for Transport) family, which mediates trafficking via MVB (multivesicular body) formation and sorting. Our studies suggest that Chmp1A is a novel tumor suppressor, especially in the pancreas. Knockdown of Chmp1A resulted in an increase of anchorage-independent growth of HEK 293T cells. Moreover, we showed that Chmp1A depleted HEK 293T cells forms tumor in xenograft mice. Knockdown of Chmp1A in PanC-1 cells promoted cell growth. In contrast, Doxycycline induced over-expression of Chmp1A in pancreatic cancer cells (PanC-1) resulted in cell growth inhibition, tumor …

Effects Of Aging And Gender On Regulators Of Muscle Adaptation In F344/Bn Rat Model, Satyanarayana Paturi

Theses, Dissertations and Capstones

Sarcopenia is the loss of muscle mass and strength that occurs with aging. Here we examine the effects of aging and gender on the regulation of molecules believed to regulate muscle growth and adaptation in the F344/BN rat. In male animals, soleus and EDL muscle/body weight ratio declined continuously with aging while muscle atrophy in female animals plateaued at 26-months and remained constant thereafter. Aging increased the phosphorylation of protein kinase-B (Akt) and the mammalian target of rapamycin (mTOR) in the female but not male soleus muscle. This finding was associated with the attenuation of muscle atrophy observed in female …

Manganese Superoxide Dismutase Contributes To Cisplatin-Induced Cytotoxicity Rather Than All-Trans Retinoic Acid-Dependent Chemoresistance, Zina-Ann Cardozo

Theses, Dissertations and Capstones

Neuroblastoma is an extra-cranial solid tumor of the nervous system occurring predominantly in infants and children younger than five years of age. Neuroblastoma presents a challenge to therapy primarily due to a decreased responsiveness to anticancer agents like cisplatin (CDDP), leading to recurrence. Vitamin A and its derivatives, known as retinoids, are preventive against cancer and induce differentiation in some cell lines. Retinoids are now being tested clinically for the treatment of neuroblastoma. One major limitation to retinoid therapy is the development of chemoresistance. In the present study human SK-N-SH neuroblastoma cells pretreated with 10 μM all-trans retinoic acid (ATRA) …

Impaired Overload-Induced Hypertrophy In Obese Zucker Rat Slow-Twitch Skeletal Muscle, Anil Kumar Gutta

Theses, Dissertations and Capstones

How insulin resistant muscle responds to mechanical overload (MOV) is not well understood. Using immunohistochemical analysis and immunoblotting, we investigated whether Lean Zucker (LZ) and insulin resistant Obese Zucker rats (OZ) respond in a similar fashion to MOV. Five young adult (2 months old) male LZ and OZ rats were subjected to a surgical ablation of the gastrocnemius muscle and overloaded for 8 weeks. MOV-induced increases in soleus muscle mass and average fiber cross-sectional area were attenuated in OZ compared to LZ animals. This reduction in OZ muscle adaptation was associated with decreased activity / phosphorylation levels of STAT3, β-catenin …