Pharmacy and Pharmaceutical Sciences Commons^™

Synthesis Of Novel Ciprofloxacin Analogues And Evaluation Of Their Anti-Proliferative Effect On Human Cancer Cell Lines, Narva Suresh, Hunsur Nagendra Nagesh, Kondapalli Venkata Govri Chandra Sekhar, Anil Kumar, Amir Nasrolahi Shirazi, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been synthesized, characterized (1H NMR, 13C NMR and LCMS) and evaluated for their inhibitory activity on the proliferation of human caucasian acute lymphoblastic leukemiacells (CCRF-CEM), breast adenocarcinoma cells (MDA-MB-468) and human colon carcinoma cells (HCT-116). Among all the synthesized ciprofloxacin analogues 3t at 50 µM showed comparable potency to doxorubicin (10mol) in all three cell lines and 3j inhibited proliferation of MDA-MB-468 up to 35% selectively over other two cell lines. Cancer is a leading cause of death worldwide. It is a group of diseases characterized by uncontrolled growth. Cancer …

In Vitro Characterization Of Avian Influenza Virus Isolates With A Truncated Ns1 Gene Segment, Aaron Dick

Honors Scholar Theses

Avian Influenza Virus represents a significant threat to the world poultry population, and is a potential threat to humans due to the possibility of cross-species AIV infection. Our approach is to characterize a number of avian virus populations with respect to their content of biologically active particles that include hemagglutinating particles (HAP), plaque forming particles (PFP), interferon inducing particles (IFP), interferon induction-suppressing particles (ISP), defective-interfering particles (DIP), cell-killing particles (CKP) and non-infectious cell killing particles (niCKP) using unique in vitro assays developed for avian influenza virus in the Marcus-Sekellick Laboratory. Specifically, we will use a strain of Avian influenza virus, …

In Vitro Anticancer Screening Of 24 Locally Used Nigerian Medicinal Plants, Saudat Adamson Fadeyi, Olugbeminiyi O. Fadeyi, Adedeji A. Adejumo, Cosmas Okoro, Elbert L. Myles

Chemistry Faculty Research

Background

Plants that are used as traditional medicine represent a relevant pool for selecting plant candidates that may have anticancer properties. In this study, the ethnomedicinal approach was used to select several medicinal plants native to Nigeria, on the basis of their local or traditional uses. The collected plants were then evaluated for cytoxicity.

Methods

The antitumor activity of methanolic extracts obtained from 24 of the selected plants, were evaluated in vitro on five human cancer cell lines.

Results

Results obtained from the plants screened indicate that 18 plant extracts of folk medicine exhibited promising cytotoxic activity against human carcinoma …

Gambogic Acid Is A Tissue-Specific Proteasome Inhibitor In Vitro And In Vivo, Xiaofen Li, Shouting Liu, Hongbiao Huang, Ningning Liu, Chong Zhao, Siyan Liao, Changshan Yang, Yurong Liu, Canguo Zhao, Shujue Li, Xiaoyu Lu, Chunjiao Liu, Lixia Guan, Kai Zhao, Xiaoqing Shi, Wenbin Song, Ping Zhou, Xiaoxian Dong, Haiping Guo, Guanmei Wen, Change Zhang, Lili Jiang, Ningfang Ma, Bing Li, Shunqing Wang, Huo Tan, Xuejun Wang, Q. Ping Dou, Jinbao Lin

Oncology Faculty Publications

Gambogic acid (GA) is a natural compound derived from Chinese herbs that has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients; however, its molecular targets have not been thoroughly studied. Here, we report that GA inhibits tumor proteasome activity, with potency comparable to bortezomib but much less toxicity. First, GA acts as a prodrug and only gains proteasome-inhibitory function after being metabolized by intracellular CYP2E1. Second, GA-induced proteasome inhibition is a prerequisite for its cytotoxicity and anticancer effect without off-targets. Finally, because expression of the CYP2E1 gene is very high in tumor tissues …

Aberrant Proliferation In Cxcr7+ Endothelial Cells Via Degradation Of The Retinoblastoma Protein, Jennifer Totonchy, Jessica M. Osborn, Sara Botto, Lisa Clepper, Ashlee V. Moses

Pharmacy Faculty Articles and Research

Angiogenesis is a critical factor in the growth and dissemination of solid tumors. Indeed, tumor vasculature is abnormal and contributes to the development and spread of malignancies by creating a hostile microenvironment. The alternative SDF-1/CXCL12 receptor, CXCR7, is frequently and specifically expressed in tumor-associated vessels. In this study, we examine the role of endothelium-expressed CXCR7 in tumor vascular dysfunction by specifically examining the contribution of CXCR7 to endothelial cell (EC) proliferation. We demonstrate that CXCR7 expression is sufficient to drive post-confluent growth in EC cultures. Further, we provide a novel mechanism for CXCR7-mediated proliferation via proteasomal degradation of the tumor …

Menthol Binding And Inhibition Of A7-Nicotinic Acetylcholine Receptors, Abrar Ashoor, Jacob C. Nordman, Daniel Veltri, Keun-Hang Susan Yang, Lina T. Al Kury, Yaroslav M. Shuba, Mohamed Magoub, Frank Christopher Howarth, Bassem Sadek, Amarda Shehu, Nadine Kabbani, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh) receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca2+-dependent Cl− channels, since menthol inhibition remained unchanged by intracellular injection of the Ca2+ chelator BAPTA and perfusion with Ca2+-free bathing solution containing …

Activation Of Amp-Activated Protein Kinase By 3,39-Diindolylmethane (Dim) Is Associated With Human Prostate Cancer Cell Death In Vitro And In Vivo, Di Chen, Sanjeev Banerjee, Qiuzhi C. Cui, Dejuan Kong, Fazlul H. Sarkar, Q. Ping Dou

Oncology Faculty Publications

There is a large body of scientific evidence suggesting that 3,39-Diindolylmethane (DIM), a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK) plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer cells. …

Quantification And In Vitro Analysis Of Nanolipoproteins (Nlps) Containing Adjuvants, Purna Venkataraman, Craig Blanchette, Nicholas O. Fischer

STAR Program Research Presentations

Nanolipoprotein particles (NLPs) self-assemble into nanoscale structures that can be used as vaccines or drug delivery agents. Due to the nature of the NLPs, a variety of immune stimulating compounds or adjuvants can be readily incorporated into NLPs: a characteristic difficult to engineer into most other nanoscale platforms. In light of this, a method for quantifying the amount adjuvant actually incorporated into NLPs is a question of high importance. Through the use of reverse phase High-Performance Liquid Chromatography (HPLC) and an Evaporative Light Scattering Detector (ELSD), standard curves can be constructed by analyzing mixtures of NLP components of known concentration, …

Plant Lectin Can Target Receptors Containing Sialic Acid, Exemplified By Podoplanin, To Inhibit Transformed Cell Growth And Migration, Jhon Ochoa-Alvarez, Harini Krishnan, Yongquan Shen, Nimish Acharya, Min Han, Dean Mcnulty, Hitoki Hasegawa

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Cancer is a leading cause of death of men and women worldwide. Tumor cell motility contributes to metastatic invasion that causes the vast majority of cancer deaths. Extracellular receptors modified by α2,3-sialic acids that promote this motility can serve as ideal chemotherapeutic targets. For example, the extracellular domain of the mucin receptor podoplanin (PDPN) is highly O-glycosylated with α2,3-sialic acid linked to galactose. PDPN is activated by endogenous ligands to induce tumor cell motility and metastasis. Dietary lectins that target proteins containing α2,3-sialic acid inhibit tumor cell growth. However, anti-cancer lectins that have been examined thus far target receptors …

Chemotherapy: The Physiological Cost Of A Cure, Megan Ellis

A with Honors Projects

This project focuses on the common long term side effects of cancer treatments, apart from cure. In addition to physiological function changes, it focuses on the chemical composition of chemotherapy drugs.

Melatonin Membrane Receptors In Peripheral Tissues: Distribution And Functions, Radomir M. Slominski, Russel J. Reiter, Natalia Schlabritz-Loutsevich, Rennolds S. Ostrom, Andrzej T. Slominski

Pharmacy Faculty Articles and Research

Many of melatonin’s actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, …

Choreographing The Adenylyl Cyclase Signalosome: Sorting Out The Partners And The Steps, Rennolds S. Ostrom, Amy S. Bogard, Robert Gros

Pharmacy Faculty Articles and Research

Adenylyl cyclases are a ubiquitous family of enzymes and are critical regulators of metabolic and cardiovascular function. Multiple isoforms of the enzyme are expressed in a range of tissues. However, for many processes, the adenylyl cyclase isoforms have been thought of as essentially interchangeable, with their impact more dependent on their common actions to increase intracellular cyclic adenosine monophosphate content regardless of the isoform involved. It has long been appreciated that each subfamily of isoforms demonstrate a specific pattern of “upstream” regulation, i.e., specific patterns of ion dependence (e.g., calcium-dependence) and specific patterns of regulation by kinases (protein kinase A …

Kshv Infection Of Endothelial Cells Manipulates Cxcr7-Mediated Signaling: Implications For Kaposi’S Sarcoma Progression And Intervention, Jennifer Totonchy, Lisa Clepper, Janet Douglas, Liron Pantanowitz, Klaus Fruh, Ashlee V. Moses

Pharmacy Faculty Articles and Research

"CXCR7 was recently characterized as an alternative receptor for the chemokine CXCL12/SDF-1, previously thought to bind and signal exclusively through CXCR4.We recently identified CXCR7 as a key cellular factor in the endothelial cell (EC) dysfunction associated with KSHV infection. CXCL12 signaling is critically associated with tumor growth, angiogenesis and metastasis in several diverse tumors and is one of the most studied chemokine/chemokine receptor interactions in cancer systems. The tumorigenic activity of the CXCL12 signaling axis offers an attractive target for therapeutic intervention in multiple cancers including Kaposi’s Sarcoma (KS). However, most of the research to date was based on the …

Simulating Molecular Mechanisms Of The Mdm2-Mediated Regulatory Interactions: A Conformational Selection Model Of The Mdm2 Lid Dynamics, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Diversity and complexity of MDM2 mechanisms govern its principal function as the cellular antagonist of the p53 tumor suppressor. Structural and biophysical studies have demonstrated that MDM2 binding could be regulated by the dynamics of a pseudo-substrate lid motif. However, these experiments and subsequent computational studies have produced conflicting mechanistic models of MDM2 function and dynamics. We propose a unifying conformational selection model that can reconcile experimental findings and reveal a fundamental role of the lid as a dynamic regulator of MDM2-mediated binding. In this work, structure, dynamics and energetics of apo-MDM2 are studied as a function of posttranslational modifications …

Library Impact Statement For Bps 555 Protein Molecular Modeling, Michael Vocino

Library Impact Statements

Library Impact Statement for BPS 555 Protein Molecular Modeling. No new resources were required to support this course.

Chemosensitization Of Cancer Cells By Sirna Using Targeted Nanogel Delivery, Erin B. Dickerson, William H. Blackburn, Michael H. Smith, Laura B. Kapa, L. Andrew Lyon, John F. Mcdonald

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background: Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics.

Methods: We report here …

Impaired M3 And Enhanced M2 Muscarinic Receptor Contractile Function In A Streptozotocin Model Of Mouse Diabetic Urinary Bladder, K. J. Pak, Rennolds S. Ostrom, M. Matsui, F. J. Ehlert

Pharmacy Faculty Articles and Research

We investigated the contractile roles of M2 and M3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M2 muscarinic receptor knockout (M2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg−1) 2–24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after …

Cytoprotective And Genoprotective Effects Of Aqueous Extracts Of Processed Pleurotus Sajor-Caju Fruiting Bodies On Hydrogen Peroxide-Induced Damage Of Human Peripheral Blood Mononuclear Cells., Mohamad Fairus Abdul Kadir

Student Works (2010-2019)

Pleurotus sajor-caju authority is one of the mushroom species that is widely grown in Malaysia. The present study was undertaken to evaluate the antioxidant, cytotoxic, cytoprotective, genotoxic and genoprotective activities of crude water extracts of this mushroom. Crude aqueous extracts were prepared from the fruiting bodies that had been processed at different temperatures such as P1: blanching (95°C ± 2°C), P2: sun drying (30°C ± 2°C), P3: freeze drying (-46°C ± 3°C) and different temperatures of oven drying (P4: 45°C, P5: 50°C, P5: 55°C and P6: 60°C ± 2°C respectively). Antioxidant capacity of all the extracts was determined using ferric …

The Guinea Pig Ileum Lacks The Direct, High-Potency, M2-Muscarinic, Contractile Mechanism Of The Mouse Ileum, Michael T. Griffin, Minoru Matsui, Rennolds S. Ostrom, Frederick J. Ehlert

Pharmacy Faculty Articles and Research

We explored whether the M2 muscarinic receptor in the guinea pig ileum elicits a highly potent, direct-contractile response, like that from the M3 muscarinic receptor knockout mouse. First, we characterized the irreversible receptor-blocking activity of 4-DAMP mustard in ileum from muscarinic receptor knockout mice to verify its M3 selectivity. Then, we used 4-DAMP mustard to inactivate M3 responses in the guinea pig ileum to attempt to reveal direct, M2 receptor-mediated contractions. The muscarinic agonist, oxotremorine-M, elicited potent contractions in ileum from wild-type, M2 receptor knockout, and M3 receptor knockout mice characterized by negative log EC50 (pEC50) values ± SEM of …

The C1 And C2 Domains Target Human Type 6 Adenylyl Cyclase To Lipid Rafts And Caveolae, Muthusamy Thangavel, Xiaoqiu Liu, Shu Qiang Sun, Joseph Kaminsky, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Previous data has shown that adenylyl cyclase type 6 (AC6) is expressed principally in lipid rafts or caveolae of cardiac myocytes and other cell types while certain other isoforms of AC are excluded from these microdomains. The mechanism by which AC6 is localized to lipid rafts or caveolae is unknown. In this study, we show AC6 is localized in lipid rafts of COS-7 cells (expressing caveolin-1) and in HEK-293 cells or cardiac fibroblasts isolated from caveolin-1 knock-out mice (both of which lack prototypical caveolins). To determine the region of AC6 that confers raft localization, we independently expressed each of the …

Oxidative Stress-Mediated Anticancer Activity Of Novel Ahr Modulators Af & 5f203, Lancelot S. Mclean

Loma Linda University Electronic Theses, Dissertations & Projects

Estrogen receptor positive (ER+) breast cancer tends to respond to anti-estrogen agents such as Tamoxifen. Approximately 40% of ER+ breast cancer is resistant to these agents and those that initially respond often acquire resistance. Estrogen receptor negative (ER-) breast cancer remains largely unresponsive to these agents. It is therefore vital to discover drugs that are potent in both forms of breast cancer. Aminoflavone, (5-amino-2, 3-fluorophenyl)-6,8-difluoro-7-methyl-4H-l-benzopyran-4-one; AF; NSC 686288) and 5F203, (2-[-Amino-3-methy phenyl]-5-flurobenzothiazole) are novel anticancer candidate agents that display potent in vitro and in vivo anti-proliferative activity against select human tumor cells with a unique anticancer activity profile in the …

Different Requirements Of The Swi/Snf Complex For Robust Nucleosome Displacement At Promoters Of Heat Shock Factor And Msn2- And Msn4-Regulated Heat Shock Genes, Tamara Y. Erkina, P. A. Tschetter, Alexander M. Erkine

Scholarship and Professional Work – COPHS

The stress response in yeast cells is regulated by at least two classes of transcription activators—HSF and Msn2/4, which differentially affect promoter chromatin remodeling. We demonstrate that the deletion of SNF2, an ATPase activity-containing subunit of the chromatin remodeling SWI/SNF complex, eliminates histone displacement, RNA polymerase II recruitment, and heat shock factor (HSF) binding at the HSP12 promoter while delaying these processes at the HSP82 and SSA4 promoters. Out of the three promoters, the double deletion of MSN2 and MSN4 eliminates both chromatin remodeling and HSF binding only at the HSP12 promoter, suggesting that Msn2/4 activators are primary determinants of …

Adenylyl Cyclase Type 6 Overexpression Selectively Enhances Ss-Adrenergic And Prostacyclin Receptor Mediated Inhibition Of Rat Cardiac Fibroblast Function Due To Co-Localization In Lipid Rafts, Xiaoqiu Liu, Muthusamy Thangavel, Shu Qiang Sun, Joseph Kaminsky, Penden Mahautmr, Jeremiah Stitham, John Hwa, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Cardiac fibroblasts produce and degrade extracellular matrix and are critical in regulating cardiac remodeling and hypertrophy. Fibroblasts are activated by factors such as transforming growth factor β and inhibited by agents that elevate 3′,5′-cyclic adenosine monophosphate (cAMP) levels. cAMP signal generation and response is known to be compartmentalized in many cell types in part through the colocalization of receptors and specific adenylyl cyclase isoforms in lipid rafts and caveolae. The present study sought to define the localization of key G protein-coupled receptors with adenylyl cyclase type 6 (AC6) in lipid rafts of rat cardiac fibroblasts and to determine if this …

In Vitro Expression And Purification Of Class I Mhc Molecules, Loi Cheng

Honors Scholar Theses

The major histocompatibility complex (MHC) is a gene family responsible for many critical functions of the immune system in most vertebrates. The MHC consists of three classes differentiated by their structure and function, and MHC class I encodes antigen binding proteins as well as chaperone and accessory proteins such as tapasin. The purpose of this project is to reconstitute several human MHC class I molecules in their peptide-filled and peptide-deficient forms, and to purify these proteins for biochemical study. The expressed proteins include wild type and mutant variants of the fusion protein human leukocyte antigen HLA-B*0801-fos, and human beta-2-microglobulin (β2m). …

Methods For The Study Of Signaling Molecules In Membrane Lipid Rafts And Caveolae, Rennolds S. Ostrom, Paul A. Insel

Pharmacy Faculty Articles and Research

Lipid rafts and caveolae are cholesterol- and sphingolipid-rich microdomains of the plasma membrane that concentrate components of certain signal transduction pathways. Interest in and exploration of these microdomains has grown in recent years, especially after the discovery of the biochemical marker of caveolae, caveolin, and the recognition that caveolin interacts with many different signaling molecules via its scaffolding domain. There are three major types of caveolins (1, 2, and 3), with some selectivity in their expression in different tissues. Results assessing lipid raft/caveolae co-localization of molecules in signal transduction pathways have provided support for the idea that signaling components are …

Nitric Oxide Inhibition Of Adenylyl Cyclase Type 6 Activity Is Dependent Upon Lipid Rafts And Caveolin Signaling Complexes, Rennolds S. Ostrom, Richard A. Bundey, Paul A. Insel

Pharmacy Faculty Articles and Research

Several cell types, including cardiac myocytes and vascular endothelial cells, produce nitric oxide (NO) via both constitutive and inducible isoforms of NO synthase. NO attenuates cardiac contractility and contributes to contractile dysfunction in heart failure, although the precise molecular mechanisms for these effects are poorly defined. Adenylyl cyclase (AC) isoforms type 5 and 6, which are preferentially expressed in cardiac myocytes, may be inhibited via a direct nitrosylation by NO. Because endothelial NO synthase (eNOS and NOS3), β-adrenergic ( AR) receptors, and AC6 all can localize in lipid raft/caveolin-rich microdomains, we sought to understand the role of lipid rafts in …

The Evolving Role Of Lipid Rafts And Caveolae In G Protein-Coupled Receptor Signaling: Implications For Molecular Pharmacology, Rennolds S. Ostrom, Paul A. Insel

Pharmacy Faculty Articles and Research

The many components of G-protein-coupled receptor (GPCR) signal transduction provide cells with numerous combinations with which to customize their responses to hormones, neurotransmitters, and pharmacologic agonists. GPCRs function as guanine nucleotide exchange factors for heterotrimeric (α, β, γ) G proteins, thereby promoting exchange of GTP for GDP and, in turn, the activation of ‘downstream’ signaling components. Recent data indicate that individual cells express mRNA for perhaps over 100 different GPCRs (out of a total of nearly a thousand GPCR genes), several different combinations of G-protein subunits, multiple regulators of G-protein signaling proteins (which function as GTPase activating proteins), and various …

Hypertonic Stress Co-Stimulates T Cell Il-2 Expression Through A Feedback Mechanism Involving Atp Release And P2 Receptor Activation Of P38 Map Kinase, William H. Loomis, Sachiko Namiki, Rennolds S. Ostrom, Paul A. Insel, Wolfgang G. Junger

Pharmacy Faculty Articles and Research

Hypertonic stress (HS) can alter the function of mammalian cells. We have reported that HS enhances differentiated responses of T cells by increasing their ability to produce interleukin (IL)-2, a finding of clinical interest because hypertonic infusions may modulate immune function in patients. HS shrinks cells and mechanically deforms membranes, which results in ATP release from many cell types. Here we investigate if ATP release is an underlying mechanism through which HS augments T cell function. We found that mechanical stress and HS induced rapid ATP release from Jurkat T cells. HS and exogenous ATP mobilized intracellular Ca2+, activated p38 …

Angiotensin Ii Enhances Adenylyl Cyclase Signaling Via Ca2+/Calmodulin. Gq-Gs Cross-Talk Regulates Collagen Production In Cardiac Fibroblasts, Rennolds S. Ostrom, Jennifer E. Naugle, Miki Hase, Caroline Gregorian, James S. Swaney, Paul A. Insel, Laurence L. Brunton, J. Gary Meszaros

Pharmacy Faculty Articles and Research

Cardiac fibroblasts regulate formation of extracellular matrix in the heart, playing key roles in cardiac remodeling and hypertrophy. In this study, we sought to characterize cross-talk between Gq and Gs signaling pathways and its impact on modulating collagen synthesis by cardiac fibroblasts. Angiotensin II (ANG II) activates cell proliferation and collagen synthesis but also potentiates cyclic AMP (cAMP) production stimulated by β-adrenergic receptors (β-AR). The potentiation of β-AR-stimulated cAMP production by ANG II is reduced by phospholipase C inhibition and enhanced by overexpression of Gq. Ionomycin and thapsigargin increased intracellular Ca2+ levels and potentiated isoproterenol- and forskolin-stimulated cAMP production, whereas …

Antioxidation Activity Of Dhea And Its Mechanisms, Sun Yang, Han Rui

Pharmacy Faculty Articles and Research

Objective: The aim of this study was to determine the anti-oxidative activity of a new chemopreventive agent--dehydroepiandrosterone (DHEA), and the mechanisms of action by which DHEA protect the thymocytes and DNA from oxidative damage. Methods: Agarose gel electrophoresis, flow cytometry, single cel! gel electrophoresis, chemiluminescence assay, triazolyl blue tetrazolumbromide (MTT) colorimetry, and three dimensional collagen gel assay were used. Results: In agarose gel electrophoresis, 10 nmol/L DHEA blocked the typical DNA degradation (DNA Ladder) induced by H₂O₂. DHEA 2. 5 nmol/L and 10 nmol/L both significantly decreased the percentage of characteristic apoptotic DNA …