Browsing by Author "San Martin, Rody"

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    5, '-ectonucleotidase mediates multiple-drug resistance in glioblastoma multiforme cells
    (2013) Quezada, Claudia; Garrido, Wallys; Oyarzún, Carlos; Fernández, Katia; Segura Segura, Rodrigo; Melo, Rómulo; Casanello Toledo, Paola Cecilia; Sobrevía Luarte, Luis Alberto; San Martin, Rody
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    Increased expression of the multidrug resistance-associated protein 1 (MRP1) in kidney glomeruli of streptozotocin-induced diabetic rats
    (WALTER DE GRUYTER GMBH, 2011) Quezada, Claudia; Alarcon, Sebastian; Carcamo, Juan G.; Yanez, Alejandro; Casanello, Paola; Sobrevia, Luis; San Martin, Rody
    Oxidative stress has been linked to the podocytopathy, mesangial expansion and progression of diabetic nephropathy. The major cell defence mechanism against oxidative stress is reduced glutathione (GSH). Some ABC transporters have been shown to extrude GSH, oxidised glutathione or their conjugates out of the cell, thus implying a role for these transporters in GSH homeostasis. We found a remarkable expression of mRNA for multidrug resistance-associated proteins (MRP/ABCC) 1, 3, 4 and 5 in rat glomeruli. Three weeks after induction of diabetes in glomeruli of streptozotocin-treated rats, we observed a decline in reduced GSH levels and an increase in the expression and activity of MRP1 (ABCC1). These lower GSH levels were improved by ex vivo treatment with pharmacological inhibitors of MRP1 activity (MK571). We conclude that increased activity of MRP1 in diabetic glomeruli is correlated with an inadequate adaptive response to oxidative stress.
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    Insulin restores glucose inhibition of adenosine transport by increasing the expression and activity of the equilibrative nucleoside transporter 2 in human umbilical vein endothelium
    (WILEY, 2006) Munoz, Gonzalo; San Martin, Rody; Farias, Marcelo; Cea, Luis; Vecchiola, Andrea; Casanello, Paola; Sobrevia, Luis
    L-Arginine transport and nitric oxide (NO) synthesis (L-arginine/NO pathway) are stimulated by insulin, adenosine or elevated extracellular D-glucose in human umbilical vein endothelial cells (HUVEC). Adenosine uptake via the human equilibrative nucleoside transporters 1 (hENT1) and 2 (hENT2) has been proposed as a mechanism regulating adenosine plasma concentration, and therefore its vascular effects in human umbilical veins. Thus, altered expression and/or activity of hENT1 or hENT2 could lead to abnormal physiological plasma adenosine level. We have characterized insulin effect on adenosine transport in HUVEC cultured in normal (5 mM) or high (25, mM) D-glucose. Insulin (1 nM) increased overall adenosine transport associated with higher hENT2-, but lower hENT1-mediated transport in normal D-glucose. insulin increased hENT2 protein abundance in normal or high D-glucose, but reduced hENT1 protein abundance in normal D-glucose. Insulin did not alter the reduced hENT1 protein abundance, but blocked the reduced hENT1 and hENT2 mRNA expression induced by high D-glucose. Insulin effect on hENT1 mRNA expression in normal D-glucose was blocked by N-G-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and mimicked by S-nitroso-N-acetyl-L,D-penicillamine (SNAP, NO donor). L-NAME did not block insulin effect on hENT2 expression. In conclusion, insulin stimulation of overall adenosine transport results from increased hENT2 expression and activity via a NO-independent mechanism. These findings could be important in hyperglycemia-associated pathological pregnancies, such as gestational diabetes, where plasma adenosine removal by the endothelium is reduced, a condition that could alter the blood flow from the placenta to the fetus affecting fetus growth and development. J. Cell. Physiol. 209: 826-835, 2006. (c) 2006 Wiley-Liss, Inc.