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Theses/Dissertations

2013

Department of Pharmacology and Toxicology

Articles 1 - 12 of 12

Full-Text Articles in Life Sciences

Insulin Treatment Attenuates Renal Adam17 And Ace2 Shedding In Akita Diabetic Mice, Esam Said Busah Salem Jan 2013

Insulin Treatment Attenuates Renal Adam17 And Ace2 Shedding In Akita Diabetic Mice, Esam Said Busah Salem

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Diabetic patients have a 40%-50% lifetime chance of developing chronic kidney disease, which remains one of the leading causes of morbidity and mortality. Alterations within renin angiotensin system balance contribute to the pathogenesis of diabetic kidney disease. Angiotensin converting enzyme 2 (ACE2) has an endogenous renoprotective role due to its ability to form angiotensin (1-7) (Ang 1-7) by degrading angiotensin II (Ang II). We have shown previously that hyperglycemia increases urinary ACE2 and albumin excretion in db/db diabetic mice. The protease, disintegrin and metalloprotease (ADAM) 17, is involved in the shedding of several transmembrane proteins, including ACE2 in ...


Chronic Swim Stress Attenuates Endocrine Response And Improves Cardiac Function In Mice Lacking The Angiotensin Ii Type 1a Receptor, Najat Khalifa Almahroug Jan 2013

Chronic Swim Stress Attenuates Endocrine Response And Improves Cardiac Function In Mice Lacking The Angiotensin Ii Type 1a Receptor, Najat Khalifa Almahroug

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Stress is a stimulus that causes an often abrupt but always large change in autonomic activity and hormone secretion. Angiotensin II (AngII) is one of the main neurohormonal mediators that are stimulated by stress. AngII mediates most of its relevant biological effects via AngII type1 receptor (AT1R) activation. Stress increases tissue and circulating levels of Ang II which contributes to stimulation of adrenal AT1R, mediating stressinduced hormone release. Ang II through the activation of AT1R not only elevates blood pressure but also has a patho-physiological relevance in cardiac remodeling. The goal of this study was to assess the influence of ...


"Characterization Of Red Diamondback Rattlesnake Venom Proteins On Cell Death And Function", Venus Ebrahimian Jan 2013

"Characterization Of Red Diamondback Rattlesnake Venom Proteins On Cell Death And Function", Venus Ebrahimian

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Snake venom is composed of many different toxins and protein components such as metalloproteases and phospholipase A2. Together, these proteins cause an up regulation in cell death pathways and disrupt the overall homeostasis of a living cell. The Red Diamondback Rattlesnake is abundantly available and well-known specie and has been used as a source for development of new drugs. It has been mainly used for the purposes of making anti-venom but it has also been therapeutically used for surgical purposes to act as an anti-aggregate. Integrins derived from RDB venom has been used for cancer cell treatment as well. Specifically ...


Locating Chelerythrine, An Alkaloid, Within A Cytosolic Environment By Maldi-Tof Mass Spectrometry, Bradley Allen Williams Jan 2013

Locating Chelerythrine, An Alkaloid, Within A Cytosolic Environment By Maldi-Tof Mass Spectrometry, Bradley Allen Williams

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The quaternary benzo-phenanthridine alkaloid (QBA) chelerythrine (CET) is a well-known inhibitor of PKC and cancer growth (Herbert et al., 1990). In human lens epithelial cells (HLECs), CET almost completely inhibits the Na+/K+ pump ATPase (NKA) without changes in phosphorylation (Lauf et al. 2013). Protein alignment studies revealed B-lymphocyte type 2 protein (Bcl-2) BH1- like motifs within the a1 subunit of the NKA to which CET, a drug mimicking Bcl-2 protein BH3-like motifs, might bind thus disrupting NKA function (Lauf et al, 2013). It is unknown by which mechanism CET crosses the plasma membrane to reach its intracellular targets, especially ...


Role Of Bax, Ibpa, Ibpb And Csph Genes In Protecting Cft073 (Uropathogenic Escherichia Coli) Against Salt And Urea Stress, Pavani Beesetty Jan 2013

Role Of Bax, Ibpa, Ibpb And Csph Genes In Protecting Cft073 (Uropathogenic Escherichia Coli) Against Salt And Urea Stress, Pavani Beesetty

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Uropathogenic Escherichia coli (UPEC) are the primary cause of 80 to 90% of uncomplicated urinary tract infections. After entering the urinary tract, uropathogenic E.coli has to tolerate high levels of salt and urea in urine to cause a successful infection. The osmotic stress imposed by urea is different from that by NaCl, as urea can freely move across the cell membrane and is a protein denaturant. Hence, microarray experiments were performed to observe the differential expression of genes in CFT073 (UPEC) due to the presence of 0.3 M NaCl and 0.6 M urea in K medium individually ...


Tolfenamic Acid Induces Cell Apoptosis And Inhibits Collagen Accumulation In Keloid Fibroblasts, Dan Yi Jan 2013

Tolfenamic Acid Induces Cell Apoptosis And Inhibits Collagen Accumulation In Keloid Fibroblasts, Dan Yi

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Keloid scar is a fibroproliferative disorder which results from the accumulation of collagen through the activation of TGF-B/Smad signaling. Tolfenamic acid (TA) has been found to inhibit collagen synthesis in animal and induce cancer cell apoptosis. In this study, we investigated the effect of DMSO on cell apoptosis, TA on collagen deposition, and TA on collagen type I and smad2 protein expression in human normal fibroblasts (NFs) and human keloid fibroblasts (KFs). In the dose- and exposure time- response assays, we found that 1% DMSO for 48h treatment did not obviously induce NF and KF apoptosis and that 0 ...


Effects Of Ang 1-7 And Endothelial Microvesicles On Ang Ii-Induced Dysfunction And Apoptosis In Cerebral Endothelial Cells, Xiang Xiao Jan 2013

Effects Of Ang 1-7 And Endothelial Microvesicles On Ang Ii-Induced Dysfunction And Apoptosis In Cerebral Endothelial Cells, Xiang Xiao

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Angiotensin II (Ang II) induces endothelial dysfunction and is implicated in the pathogenesis of vascular diseases. Angiotensin 1-7 (Ang 1-7) has been reported to counteract many deleterious effects of Ang II. Endothelial microvesicles (EMVs) are small membrane vesicles released from endothelial cells (ECs) undergoing stress and apoptosis. But their functions are largely unknown. In this study, we investigated the effects of Ang 1-7 and EMVs on apoptosis and dysfunction of human brain microvascular endothelial cells (HbmECs). Reactive oxygen species (ROS) and nitric oxide (NO) production, and Nox2, p-Akt/Akt, p-eNOS/eNOS expression were analyzed. We found that Ang II dose-dependently ...


Physical Exercise Training But Not Metformin Attenuates Albuminuria And Shedding Of Ace2 In Type 2 Diabetic Db/Db Mice, Hari Krishna Somineni Jan 2013

Physical Exercise Training But Not Metformin Attenuates Albuminuria And Shedding Of Ace2 In Type 2 Diabetic Db/Db Mice, Hari Krishna Somineni

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Angiotensin II (Ang II), a potent vasoconstrictor cleaved from Ang I, is responsible for renal damage in diabetes. Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and has been shown to be renoprotective by degrading Ang II to Ang-(1-7). A Disintegrin and Metalloproteinases (ADAMs) were recently identified as an ectodomain sheddases of transmembrane proteins. ADAM17 mediated shedding of renal ACE2 could contribute to the pathogenesis of diabetic nephropathy. In our previous study, rosiglitazone treatment normalized hyperglycemia and improved renal injury by preventing ACE2 shedding. The aim of this study is to test the hypothesis that improved ...


Bioaccumulation And Neuroinflammation Of Gold Nanoparticles In The Central Nervous System, Fahimeh Fallahi Jan 2013

Bioaccumulation And Neuroinflammation Of Gold Nanoparticles In The Central Nervous System, Fahimeh Fallahi

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Gold nanoparticles (GNPs) possess unique physicochemical properties that may facilitate entry into the central nervous system (CNS) where they may act therapeutically. There is little information on biodistribution or inflammatory effects of GNPs in specific brain regions. Brain Localization and neuroinflammatory response to citrate-capped spherical GNP (10 nm) was determined 24 hours after intravenous (IV) injection in male C57Bl mice. A known inflammogen, lipopolysaccharide (LPS, 2 mg kg-1, SC), was tested as a positive control supplement. Aggregation of GNPs was measured using various Phosphate-Buffered Saline (PBS) concentrations (10, 1, 0.1, 0.01 X) to determine the optimal buffer concentration ...


K-Cl Cotransport: Role Of Kcc3 In Cellular Potassium (K) Homeostasis In Kcc3- Transfected Hek-293 Cells, Nagendra Babu Ravilla Jan 2013

K-Cl Cotransport: Role Of Kcc3 In Cellular Potassium (K) Homeostasis In Kcc3- Transfected Hek-293 Cells, Nagendra Babu Ravilla

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K-Cl cotransport (KCC) mediated by four protein isoforms, KCC1 to KCC4, plays a significant role in cell volume regulation, and in K and Cl homeostasis. In this study, we demonstrate the importance of KCC3 and its two threonine (T) phosphorylation sites T991 and T1048 in cellular K homeostasis in isogenic human embryonic kidney (HEK-293) cells transfected with KCC3 wild type (WT) or constitutively active double mutant KCC3 (AA) expressed under tetracycline or doxycycline control. In both WT and AA cells, under baseline conditions, the Na-K-2Cl cotransport (NKCC) (55 %- 60 %) was the major contributor of Rb influx followed by the Na ...


Effects Of Red Diamondback Rattlesnake Venom On Keloid Dermal Fibroblasts In Vitro, Mackenzie Shelby Newman Jan 2013

Effects Of Red Diamondback Rattlesnake Venom On Keloid Dermal Fibroblasts In Vitro, Mackenzie Shelby Newman

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Keloid scarring is an inflammatory healing response to physical injury such as incision or piercing in the dermis. It is characterized by aberrant extracellular matrix production, the overaccumulation of mature collagen, and excessive fibroblast proliferation and migration beyond the borders of the original wound site. This results in swelling, depigmentation, itchiness, and pain akin to a benign tumor. Although there are myriad treatments for the condition, most are invasive and exhibit a high recurrence rate. Previous studies have shown that rattlesnake venom stimulates apoptosis in the skin via multiple specific mechanisms, largely composed of extracellular matrix and its receptors' interactions ...


The Aryl Hydrocarbon Receptor Regulates An Essential Transcriptional Element In The Immunoglobulin Heavy Chain Gene, Michael J. Wourms Jan 2013

The Aryl Hydrocarbon Receptor Regulates An Essential Transcriptional Element In The Immunoglobulin Heavy Chain Gene, Michael J. Wourms

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that inhibits immunoglobulin (Ig) expression and Ig heavy (IgH) chain gene transcription. Transcription of the IgH gene involves several regulatory elements including the 3'lgh regulatory region (3'lghRR) which is composed of four enhancers (hs3A, hs1,2, hs4, and hs3B). Dioxin responsive elements (DRE) in the hs4 and hs1,2 enhancers of the 3lghRR that bind the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates dioxin sensitive genes suggest that the 3'lghRR may be a transcriptional target of TCDD. The current study ...