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Richmond, VA, United States

Pullen N.A.,Virginia Commonwealth University | Anand M.,Virginia Commonwealth University | Cooper P.S.,Veterans Affairs ire Medical Center | Fillmore H.L.,Virginia Commonwealth University | Fillmore H.L.,Old Dominion University
Journal of Neuro-Oncology | Year: 2012

Herein we continue the study of matrix metalloproteinase- 1 (MMP-1) with respect to glioblastoma multiforme (GBM) cell tumorigenicity and angiogenesis. A model of tumorigenicity with cells stably altered to over-express or knock-down MMP-1 revealed that it significantly increases tumor incidence and size. Organized endothelial growth in human umbilical vein endothelial cell (HUVEC)-GBM cocultures was significantly increased in the presence ofMMP- 1. CD31 analysis of model tumors elucidated a substantial recruitment of endothelium in MMP-1 enhanced samples. Antibody arrays indicated an inverse expression of certain anti-angiogenic factors with respect to MMP-1, the most notable of which was a significant increase in tissue inhibitor of metalloproteinases-4 (TIMP-4) in the absence of MMP-1, as validated by immunoblot. © 2011 Springer Science+Business Media, LLC.

Ridlon J.M.,Virginia Commonwealth University | Ridlon J.M.,Veterans Affairs ire Medical Center | Ikegawa S.,Kinki University | Alves J.M.P.,Virginia Commonwealth University | And 13 more authors.
Journal of Lipid Research | Year: 2013

Clostridium scindens American Type Culture Collection 35704 is capable of converting primary bile acids to toxic secondary bile acids, as well as converting glucocorticoids to androgens by side-chain cleavage. The molecular structure of the side-chain cleavage product of cortisol produced by C. scindens was determined to be 11 β-hydroxyandrost- 4-ene-3,17-dione (11 β-OHA) by high-resolution mass spectrometry, 1H and 13C NMR spectroscopy, and X-ray crystallography. Using RNA-Seq technology, we identified a cortisol-inducible ( ~ 1,000-fold) operon ( des ABCD) encoding at least one enzyme involved in anaerobic side-chain cleavage. The des C gene was cloned, overexpressed, purified, and found to encode a 20α-hydroxysteroid dehydrogenase (HSDH). This operon also encodes a putative " transketolase" ( des AB) hypothesized to have steroid-17,20-desmolase/ oxidase activity, and a possible corticosteroid transporter ( des D). RNA-Seq data suggests that the two-carbon side chain of glucocorticords may feed into the pentose-phosphate pathway and are used as a carbon source. The 20 α-HSDH is hypothesized to function as a metabolic "rheostat" controlling rates of side-chain cleavage. Phylogenetic analysis suggests this operon is rare in nature and the des C gene evolved from a gene encoding threonine dehydrogenase. The physiological effect of 11 β-OHAD on the host or other gut microbes is currently unknown. Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc.

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