@article {1505,
	title = {Identification of sokotrasterol sulfate as a novel proangiogenic steroid},
	journal = {Circulation Research},
	volume = {99},
	number = {3},
	year = {2006},
	note = {ISI Document Delivery No.: 070DTTimes Cited: 3Cited Reference Count: 39Murphy, Siun Larrivee, Bruno Pollet, Ingrid Craig, Kyle S. Williams, David E. Huang, Xin-Hui Abbott, Megan Wong, Fred Curtis, Cameron Conrads, Thomas P. Veenstra, Timothy Puri, Mira Hsiang, York Roberge, Michel Andersen, Raymond J. Karsan, Aly},
	month = {Aug},
	pages = {257-265},
	type = {Article},
	abstract = {The potential to promote neovascularization in ischemic tissues using exogenous agents has become an exciting area of therapeutics. In an attempt to identify novel small molecules with angiogenesis promoting activity, we screened a library of natural products and identified a sulfated steroid, sokotrasterol sulfate, that induces angiogenesis in vitro and in vivo. We show that sokotrasterol sulfate promotes endothelial sprouting in vitro, new blood vessel formation on the chick chorioallantoic membrane, and accelerates angiogenesis and reperfusion in a mouse hindlimb ischemia model. We demonstrate that sulfation of the steroid is critical for promoting angiogenesis, as the desulfated steroid exhibited no endothelial sprouting activity. We thus developed a chemically synthesized sokotrasterol sulfate analog, 2 beta,3 alpha,6 alpha-cholestanetrisulfate, that demonstrated equivalent activity in the hindlimb ischemia model and resulted in the generation of stable vessels that persisted following cessation of therapy. The function of sokotrasterol sulfate was dependent on cyclooxygenase-2 activity and vascular endothelial growth factor induction, as inhibition of either cyclooxygenase-2 or vascular endothelial growth factor blocked angiogenesis. Surface expression of alpha(v)beta(3) integrin was also necessary for function, as neutralization of alpha(v)beta(3) integrin, but not beta(1) integrin, binding abrogated endothelial sprouting and antiapoptotic activity in response to sokotrasterol sulfate. Our findings indicate that sokotrasterol sulfate and its analogs can promote angiogenesis in vitro and in vivo and could potentially be used for promoting neovascularization to relieve the sequelae of vasoocclusive diseases.},
	keywords = {ACTIVATION, ANGIOGENESIS, apoptosis, ARTERIOGENESIS, ENDOTHELIAL-CELLS, endothelium, IN-VITRO, INHIBITION, INTEGRIN ALPHA(V)BETA(3), ischemia, MARINE NATURAL-PRODUCTS, NF-KAPPA-B},
	isbn = {0009-7330},
	url = {<Go to ISI>://000239501200009},
	author = {Murphy, S. and Larrivee, B. and Pollet, I. and Craig, K. S. and Williams, D. E. and Huang, X. H. and Abbott, M. and Wong, F. and Curtis, C. and Conrads, T. P. and Veenstra, T. and Puri, M. and Hsiang, Y. and Roberge, M. and Andersen, R. J. and Karsan, A.}
}
@article {5130,
	title = {Arsenicals inhibit thioredoxin reductase in cultured rat hepatocytes},
	journal = {Chemical Research in Toxicology},
	volume = {14},
	number = {3},
	year = {2001},
	note = {ISI Document Delivery No.: 415LTTimes Cited: 86Cited Reference Count: 46},
	month = {Mar},
	pages = {305-311},
	type = {Article},
	abstract = {Thioredoxin reductase (TR), an NADPH-dependent flavoenzyme that catalyzes the reduction of many disulfide-containing substrates, plays an important role in the cellular response to oxidative stress. Trivalent arsenicals, especially methyl As that contains trivalent arsenic (MAsIII), are potent noncompetitive inhibitors of TR purified from mouse liver. Because MAsIII is produced in the biomethylation of As, it was postulated that the extent of inhibition of TR in cultured rat hepatocytes would correlate with the intracellular concentration of methyl As. Exposure of cultured hepatocytes to inorganic As-III (iAs(III)), MAsIII, or aurothioglucose (ATG, a competitive inhibitor of TR activity) for 30 min caused a concentration-dependent reduction in TR activity. The estimated IC50 was much greater than 100 muM for iAS(III), similar to 10 muM for ATG, and similar to3 muM for MAsIII. In hepatocytes exposed to 1 muM MAsIII for up to 24 h, the inhibition of TR activity was maximal (similar to 40\%) after exposure for 15 min. After exposure for 3 h [when most MAsIII has been converted to dimethyl As (DMAs)], TR activity in these cells had returned to control levels. Notably, exposure of the cell to 50 muM DMAsIII did not affect TR activity. In hepatocytes exposed to 10 muM iAs(III) for up to 24 h, the inhibition of TR activity was progressive; at 24 h, activity was reduced similar to 35\%. Following exposure to iAsIII or MAsIII, the extent of inhibition of TR activity correlated strongly with the intracellular concentration of MAs. Taken together, these results suggest that arsenicals formed in the course of cellular metabolism of As are potent inhibitors of TR activity. In particular, MAsIII, an intermediate in the metabolic pathway, is an especially potent inhibitor of TR. Hence, the capacity of cells to produce or consume the intermediates in the pathway for As methylation may be an important determinant of susceptibility to the toxic effects of As.},
	keywords = {apoptosis, ENZYMATIC REDUCTION, IN-VITRO METHYLATION, LIVER, MAMMALIAN SYSTEMS, MONOMETHYLARSONOUS ACID MMA(III), NF-KAPPA-B, RABBIT ERYTHROCYTES, REDOX, REGULATION, SUBSTRATE},
	isbn = {0893-228X},
	url = {<Go to ISI>://000167723600007},
	author = {Lin, S. and Del Razo, L. M. and Styblo, M. and Wang, C. Q. and Cullen, W. R. and Thomas, D. J.}
}
