Application of a high-content multiparameter cytotoxicity assay to prioritize compounds based on toxicity potential in humans.
AuthorsAbraham VC, Towne DL, Waring JF, Warrior U, Burns DJ,
JournalJ Biomol Screen
PubMed ID18566484
'Prioritization of compounds based on human hepatotoxicity potential is currently a key unmet need in drug discovery, as it can become a major problem for several lead compounds in later stages of the drug discovery pipeline. The authors report the validation and implementation of a high-content multiparametric cytotoxicity assay based ... More
Activator of G protein signaling 3 promotes epithelial cell proliferation in PKD.
AuthorsNadella R, Blumer JB, Jia G, Kwon M, Akbulut T, Qian F, Sedlic F, Wakatsuki T, Sweeney WE, Wilson PD, Lanier SM, Park F,
JournalJ Am Soc Nephrol
PubMed ID20488951
'The activation of heterotrimeric G protein signaling is a key feature in the pathophysiology of polycystic kidney diseases (PKD). In this study, we report abnormal overexpression of activator of G protein signaling 3 (AGS3), a receptor-independent regulator of heterotrimeric G proteins, in rodents and humans with both autosomal recessive and ... More
The matricellular protein cysteine-rich protein 61 (CCN1/Cyr61) enhances physiological adaptation of retinal vessels and reduces pathological neovascularization associated with ischemic retinopathy.
AuthorsHasan A, Pokeza N, Shaw L, Lee HS, Lazzaro D, Chintala H, Rosenbaum D, Grant MB, Chaqour B,
JournalJ Biol Chem
PubMed ID21212276
'Retinal vascular damages are the cardinal hallmarks of retinopathy of prematurity (ROP), a leading cause of vision impairment and blindness in childhood. Both angiogenesis and vasculogenesis are disrupted in the hyperoxia-induced vaso-obliteration phase, and recapitulated, although aberrantly, in the subsequent ischemia-induced neovessel formation phase of ROP. Yet, whereas the histopathological ... More
Selective blockade of cytoskeletal actin remodeling reduces experimental choroidal neovascularization.
AuthorsCaballero S, Yang R, Grant MB, Chaqour B,
JournalInvest Ophthalmol Vis Sci
PubMed ID21178140
'The efficacy of the peptide Ac-EEED on reducing cell adhesion and proliferation in vitro and choroidal neovascularization (CNV) in vivo was examined. The peptide chimera containing the Ac-EEED sequence was chemically linked to the N terminus of the XMTM delivery peptide from the E(rns) viral surface protein. Ac-EEED or scrambled ... More
Loss of activator of G-protein signaling 3 impairs renal tubular regeneration following acute kidney injury in rodents.
The intracellular mechanisms underlying renal tubular epithelial cell proliferation and tubular repair following ischemia-reperfusion injury (IRI) remain poorly understood. In this report, we demonstrate that activator of G-protein signaling 3 (AGS3), an unconventional receptor-independent regulator of heterotrimeric G-protein function, influences renal tubular regeneration following IRI. In rat kidneys exposed to ... More
Osteoconductivity and growth factor production by MG63 osteoblastic cells on bioglass-coated orthopedic implants.
AuthorsTan F, Naciri M, Al-Rubeai M,
JournalBiotechnol Bioeng
PubMed ID20872820
We have produced Bioglass coatings for Orthopedic implants by using a novel coating technique, CoBlast. The two resultant surfaces, designated BG and hydroxyapatite (HA)/BG, were compared with their HA counterpart, OsteoZip in terms of osteoblastic cell attachment, adhesion, proliferation, differentiation, and growth factor production. BG and HA/BG were demonstrated by ... More
Interplay between REST and nucleolin transcription factors: a key mechanism in the overexpression of genes upon increased phosphorylation.
AuthorsTediose T, Kolev M, Sivasankar B, Brennan P, Morgan BP, Donev R,
JournalNucleic Acids Res
PubMed ID20100803
Non-malignant cells can be transformed via the activation of kinases that control degradation of neural-restrictive silencer factor (REST). Here, we identify a mechanism that contributes to the activation of genes, expression of which is controlled by responsive elements containing overlapping binding sites for REST and nucleolin. We demonstrate that both ... More