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2013

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Full-Text Articles in Cells

Centrosomal Kinase Nek2 Cooperates With Oncogenic Pathways To Promote Metastasis, T K. Das, Dibyendu Dana, Suneeta S. Paroly, S. K. Perumal, S. Singh, H. Jhun, J. Pendse, R. L. Cagan, T. T. Talele, Sanjai Kumar Sep 2013

Centrosomal Kinase Nek2 Cooperates With Oncogenic Pathways To Promote Metastasis, T K. Das, Dibyendu Dana, Suneeta S. Paroly, S. K. Perumal, S. Singh, H. Jhun, J. Pendse, R. L. Cagan, T. T. Talele, Sanjai Kumar

Publications and Research

Centrosomal kinase Nek2 is overexpressed in different cancers, yet how it contributes toward tumorigenesis remains poorly understood. dNek2 overexpression in a Drosophila melanogaster model led to upregulation of Drosophila Wnt ortholog wingless (Wg), and alteration of cell migration markers—Rho1, Rac1 and E-cadherin (Ecad)—resulting in changes in cell shape and tissue morphogenesis. dNek2 overexpression cooperated with receptor tyrosine kinase and mitogen-activated protein kinase signaling to upregulate activated Akt, Diap1, Mmp1 and Wg protein to promote local invasion, distant seeding and metastasis. In tumor cell injection assays, dNek2 cooperated with Ras and Src signaling to promote aggressive colonization of tumors into different …


Sparstolonin B Inhibits Pro-Angiogenic Functions And Blocks Cell Cycle Progression In Endothelial Cells, H. R. Bateman, Q. Liang, D. Fan, V. Rodriguez, Susan M. Lessner Aug 2013

Sparstolonin B Inhibits Pro-Angiogenic Functions And Blocks Cell Cycle Progression In Endothelial Cells, H. R. Bateman, Q. Liang, D. Fan, V. Rodriguez, Susan M. Lessner

Faculty Publications

Sparstolonin B (SsnB) is a novel bioactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including diabetic retinopathy, tumor growth, and atherosclerosis. In functional assays, SsnB inhibited endothelial cell tube formation (Matrigel method) and cell migration (Transwell method) in a dose-dependent manner. Microarray experiments with human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) demonstrated differential expression of several hundred genes in response to SsnB exposure (916 and 356 …


Withaferin A Effectively Targets Soluble Vimentin In The Glaucoma Filtration Surgical Model Of Fibrosis, Paola Bargagna-Mohan, Sunil P. Deokule, Kyle G. Thompson, John Wizeman, Cidambi Srinivasan, Sunil Vooturi, Uday B. Kompella, Royce Mohan May 2013

Withaferin A Effectively Targets Soluble Vimentin In The Glaucoma Filtration Surgical Model Of Fibrosis, Paola Bargagna-Mohan, Sunil P. Deokule, Kyle G. Thompson, John Wizeman, Cidambi Srinivasan, Sunil Vooturi, Uday B. Kompella, Royce Mohan

Ophthalmology and Visual Science Faculty Publications

Withaferin A (WFA) is a natural product that binds to soluble forms of the type III intermediate filament (IF) vimentin. Currently, it is unknown under what pathophysiological contexts vimentin is druggable, as cytoskeltal vimentin-IFs are abundantly expressed. To investigate druggability of vimentin, we exploited rabbit Tenon's capsule fibroblast (RbTCF) cell cultures and the rabbit glaucoma filtration surgical (GFS) model of fibrosis. WFA potently caused G₀/G₁ cell cycle inhibition (IC₅₀ 25 nM) in RbTCFs, downregulating ubiquitin E3 ligase skp2 and inducing p27(Kip1) expression. Transforming growth factor (TGF)-ß-induced myofibroblast transformation caused development of cell spheroids with numerous elongated invadopodia, which WFA blocked …


Hydroxylamine Acutely Activates Glucose Uptake In L929 Fibroblast Cells, Larry L. Louters, Jared P. Scripture, David P. Kuipers, Stephen M. Gunnink Apr 2013

Hydroxylamine Acutely Activates Glucose Uptake In L929 Fibroblast Cells, Larry L. Louters, Jared P. Scripture, David P. Kuipers, Stephen M. Gunnink

University Faculty Publications and Creative Works

Nitroxyl (HNO) has a unique, but varied, set of biological properties including beneficial effects on cardiac contractility and stimulation of glucose uptake by GLUT1. These biological effects are largely initiated by HNO's reaction with cysteine residues of key proteins. The intracellular production of HNO has not yet been demonstrated, but the small molecule, hydroxylamine (HA), has been suggested as possible intracellular source. We examined the effects of this molecule on glucose uptake in L929 fibroblast cells. HA activates glucose uptake from 2 to 5-fold within two minutes. Prior treatment with thiol-active compounds, such as iodoacetamide (IA), cinnamaldehyde (CA), or phenylarsine …


Differential Regulation Of Glut1 Activity In Human Corneal Limbal Epithelial Cells And Fibroblasts, David P. Kuipers, Jared P. Scripture, Stephen M. Gunnink, Matthew J. Salie Feb 2013

Differential Regulation Of Glut1 Activity In Human Corneal Limbal Epithelial Cells And Fibroblasts, David P. Kuipers, Jared P. Scripture, Stephen M. Gunnink, Matthew J. Salie

University Faculty Publications and Creative Works

The corneal epithelial tissue is a layer of rapidly growing cells that are highly glycolytic and express GLUT1 as the major glucose transporter. It has been shown that GLUT1 in L929 fibroblast cells and other cell lines can be acutely activated by a variety agents. However, the acute regulation of glucose uptake in corneal cells has not been systematically investigated. Therefore, we examined glucose uptake in an immortalized human corneal-limbal epithelial (HCLE) cell line and compared it to glucose uptake in L929 fibroblast cells, a cell line where glucose uptake has been well characterized. We report that the expression of …


Non-Motile Primary Cilia As Fluid Shear Stress Mechanosensors, Surya M. Nauli, Xingjian Jin, Wissam A. Aboualaiwi, Wassim El-Jouni, Xuefeng Su, Jing Zhou Jan 2013

Non-Motile Primary Cilia As Fluid Shear Stress Mechanosensors, Surya M. Nauli, Xingjian Jin, Wissam A. Aboualaiwi, Wassim El-Jouni, Xuefeng Su, Jing Zhou

Pharmacy Faculty Articles and Research

Primary cilia are sensory organelles that transmit extracellular signals into intracellular biochemical responses. Structural and functional defects in primary cilia are associated with a group of human diseases, known as ciliopathies, with phenotypes ranging from cystic kidney and obesity to blindness and mental retardation. Primary cilia mediate mechano- and chemosensation in many cell types. The mechanosensory function of the primary cilia requires the atypical G-protein-coupled receptor polycystin-1 and the calcium-permeable nonselective cation channel polycystin-2. Mechanical stimulations such as fluid-shear stress of the primary cilia initiate intracellular calcium rise, nitric oxide release, and protein modifications. In this review, we describe a …


Membrane Surface Charges Attracted Protons Are Not Relevant To Proton Motive Force, James Weifu Lee Jan 2013

Membrane Surface Charges Attracted Protons Are Not Relevant To Proton Motive Force, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

[First Paragraph] Only a half-century ago, British scientist Peter Mitchell proposed the conceptual scheme known as "chemiosmotic theory" that identified the role of proton coupling in the formation of ATP in cells [1,2]. Mitchell's delocalized proton-coupling chemiosmotic theory was initially quite controversial. But it would win for him the Nobel Prize in Chemistry in 1978. However, questions about Mitchell's chemiosmotic hypothesis have never gone away and a number of credible studies indicated the full extent of Mitchell's idea didn't always hold up to experience.


The Roles Of Primary Cilia In Polycystic Kidney Disease, Samred H. Kathem, Ashraf M. Mohieldin, Surya M. Nauli Jan 2013

The Roles Of Primary Cilia In Polycystic Kidney Disease, Samred H. Kathem, Ashraf M. Mohieldin, Surya M. Nauli

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited genetic disorder that results in progressive renal cyst formation with ultimate loss of renal function and other systemic disorders. These systemic disorders include abnormalities in cardiovascular, portal, pancreatic and gastrointestinal systems. ADPKD is considered to be among the ciliopathy diseases due to the association with abnormal primary cilia function. In order to understand the full course of primary cilia and its association with ADPKD, the structure, functions and role of primary cilia have been meticulously investigated. As a result, the focus on primary cilia has emerged to support the vital roles …