Medical Biochemistry Commons^™

Na/K-Atpase Signaling And Salt Sensitivity: The Role Of Oxidative Stress, Jiang Liu, Yanling Yan, Ying Nie

Biochemistry and Microbiology

Other than genetic regulation of salt sensitivity of blood pressure, many factors have been shown to regulate renal sodium handling which contributes to long-term blood pressure regulation and have been extensively reviewed. Here we present our progress on the Na/K-ATPase signaling mediated sodium reabsorption in renal proximal tubules, from cardiotonic steroids-mediated to reactive oxygen species (ROS)-mediated Na/K-ATPase signaling that contributes to experimental salt sensitivity.

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Biochemistry and Microbiology

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed …

Helicobacter-Pylori Negative Gastritis In Children—A New Clinical Enigma, Yoram Elitsur, Deborah L. Preston

Biochemistry and Microbiology

The decrease in the prevalence of Helicobacter pylori (Hp) infection in children in the world gave rise to a new pathological finding termed as Hp-negative gastritis. Unfortunately, the term “Hp-negative gastritis” has not been identified as a pathological process and has the status of a “second cousin”; in most publications it was never mentioned as a subject to be dealt with, but was “left over” data that was never the topic of the manuscripts’ discussions. Only recently has the topic captured the attention of the pathologists who described this phenomenon in adults, yet the pathological and/or clinical spectrum or significance …

Antioxidants Condition Pleiotropic Vascular Responses To Exogenous H2o2: Role Of Modulation Of Vascular Tp Receptors And The Heme Oxygenase System, Nitin Puri, Fan Zhang, Sumit R. Monu, Komal R. Sodhi, Lars Bellner, Brian D. Lamon, Yilun Zhang, Nader G. Abraham, Alberto Nasjletti

Biochemistry and Microbiology

Aims: Hydrogen peroxide (H(2)O(2)), a nonradical oxidant, is employed to ascertain the role of redox mechanisms in regulation of vascular tone. Where both dilation and constriction have been reported, we examined the hypothesis that the ability of H(2)O(2) to effect vasoconstriction or dilation is conditioned by redox mechanisms and may be modulated by antioxidants.

Results: Exogenous H(2)O(2) (0.1-10.0 μM), dose-dependently reduced the internal diameter of rat renal interlobular and 3rd-order mesenteric arteries (p<0.05). This response was obliterated in arteries pretreated with antioxidants, including tempol, pegylated superoxide dismutase (PEG-SOD), butylated hydroxytoluene (BHT), and biliverdin (BV). However, as opposed to tempol or PEG-SOD, BHT & BV, antioxidants targeting radicals downstream of H(2)O(2), also uncovered vasodilation.

Innovations: Redox-dependent vasoconstriction to H(2)O(2) was blocked by inhibitors of cyclooxygenase (COX) (indomethacin-10 μM), thromboxane (TP) synthase (CGS13080-10 μM), and TP receptor antagonist (SQ29548-1 μM). However, H(2)O(2) …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana A. Akinsete, Gabriela Ion, Theodore R. Witte, W. Elaine Hardman

Biochemistry and Microbiology

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

Effects Of Canola And Corn Oil Mimetic On Jurkat Cells, Gabriela Ion, Kayla Fazio, Juliana A. Akinsete, W. Elaine Hardman

Biochemistry and Microbiology

BACKGROUND: The Western diet is high in omega-6 fatty acids and low in omega-3 fatty acids. Canola oil contains a healthier omega 3 to omega 6 ratio than corn oil. Jurkat T leukemia cells were treated with free fatty acids mixtures in ratios mimicking that found in commercially available canola oil (7% α-linolenic, 30% linoleic, 54% oleic) or corn oil (59% linoleic, 24% oleic) to determine the cell survival or cell death and changes in expression levels of inflammatory cytokines and receptors following oil treatment.

METHODS: Fatty acid uptake was assessed by gas chromatography. Cell survival and cell death were …

Dysglycemia Induces Abnormal Circadian Blood Pressure Variability, Sivarajan Kumarasamy, Kathirvel Gopalakrishnan, Dong Hyun Kim, Nader G. Abraham, William D. Johnson, Bina Joe, Alok K. Gupta

Biochemistry and Microbiology

Background: Prediabetes (PreDM) in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV).

Hypothesis: Systemic inflammation and glycemia influence circadian blood pressure variability.

Methods: Dahl salt-sensitive (S) rats (n = 19) after weaning were fed either an American (AD) or a standard (SD) diet. The AD (high-glycemic-index, high-fat) simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat) mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG), adipokines (leptin and adiponectin), and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) …

Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman

Biochemistry and Microbiology

Background: Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring.

Methods: Female SV 129 mice were divided into two groups and placed on …

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Biochemistry and Microbiology

Background

Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas.

Results

HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …

High Dietary Level Of Synthetic Vitamin E On Lipid Peroxidation, Membrane Fatty Acid Composition And Cytotoxicity In Breast Cancer Xenograft And In Mouse Host Tissue, Ivan L. Cameron, Jesus Munoz, Christopher J. Barnes, W. Elaine Hardman

Biochemistry and Microbiology

Background

d-α-tocopherol is a naturally occurring form of vitamin E not previously known to have antitumor activity. Synthetic vitamin E (sE) is a commonly used dietary supplement consisting of a mixture of d-α-tocopherol and 7 equimolar stereoisomers. To test for antilipid peroxidation and for antitumor activity of sE supplementation, two groups of nude mice bearing a MDA-MB 231 human breast cancer tumor were fed an AIN-76 diet, one with and one without an additional 2000 IU/kg dry food (equivalent to 900 mg of all-rac-α-tocopherol or sE). This provided an intake of about 200 mg/kg body weight per day. The mice …

Murine Epidermal Cell Antigen (Skn)-Directed Autoimmunity Induced By Transfer Of Cd4+ T Cells, Susan H. Jackman, Shivaleela Keerthy, Giselle Perry

Biochemistry and Microbiology

While pathogenic T cells have been identified for several diseases with epithelial cell damage, an autoimmune T cell-mediated response targeted against a known keratinocyte antigen has not been reported. Previously we described an autoimmune response directed to the mouse epidermal cell antigens, Skn. For our murine model, primed Skn-immune lymphocytes are adoptively transferred to recipients, which develop lesions at the site of mild skin trauma. In this study we investigated the nature of the autoimmune component of the Skn response. A time-course study demonstrated a relationship between the number of primed Sknimmune cells injected and the severity of skin lesions …