Mechanisms by which the dithiol chelating agent 2, 3-dimercaptopropane-1-sulfonate (DMPS) significantly alters the renal tubular transport, accumulation, and toxicity of inorganic mercury were studied in isolated perfused pars recta (S2) segments of proximal tubules of rabbits. Addition of 200 microM DMPS to the bath provided complete protection from the toxic effects of 20 microM inorganic mercury in the lumen. The protection was linked to decreased uptake and accumulation of mercury. Additional data indicated that, when DMPS and inorganic mercury were coperfused through the lumen, very little inorganic mercury was taken up from the lumen. We also obtained data indicating that DMPS is transported by the organic anion transport system and that this transport is linked to the therapeutic effects of DMPS. Interestingly, very little inorganic mercury was taken up and no cellular pathological changes were detected when inorganic mercury and DMPS were added to the bath. We also tested the hypothesis that DMPS can extract cellular mercury while being transported from the bath into the luminal compartment. Our findings showed that, when DMPS was applied to the basolateral membranes of S2 segments after they had been exposed to mercuric conjugates of glutathione of the laminal membrane, the tubular content of mercury was greatly reduced and the rates of disappearance of mercury from the lumen changed from positive values to markedly negative values. We conclude that inorganic mercury is extracted from proximal tubular cells by a transport process involving the movement of DMPS from the bathing compartment to the luminal compartment.
This study was designed to examine the synthesis and possible secretion of glutathione (GSH) in the S1, S2, and S3 segments of the rabbit proximal tubule. GSH synthesis and secretion rates were measured in the three segments of the proximal tubule, using the isolated perfused renal tubule technique. Tritiated (3H) glycine was perfused into segments and synthesized[Formula: see text]GSH (3H on the glycine residue) was measured in the bathing solution, collectate, and tubule extract. In the S1 segments, GSH was synthesized at the rate of 8.65 ± 0.88 fmol ⋅ min−1 ⋅ mm−1tubule length and preferentially secreted into the lumen at the rate of 7.28 ± 0.74 fmol ⋅ min−1 ⋅ mm−1. The difference between synthesis and secretion appeared in the bathing solution. The S2 segment synthesized GSH at the rate of 3.88 ± 0.82 and secreted GSH at the rate of 2.78 ± 0.57 fmol ⋅ min−1 ⋅ mm−1. GSH synthesis and secretion rates in the S3 segment were 5.45 ± 1.19 and 4.22 ± 1.16 fmol ⋅ min−1 ⋅ mm−1, respectively. Cellular concentrations of[Formula: see text]GSH increased along the length of the proximal tubule, with the highest concentrations in the S3 segment. The respective GSH cellular concentrations in the S1, S2, and S3 segments were 35.89 ± 10.51, 49.65 ± 9.32, and 116.90 ± 15.76 μM. These findings indicate that there is heterogeneity of GSH synthesis along the proximal tubule and that synthesized GSH is secreted preferentially into the lumen.
Longtime FQ Editorial Board member and 2018 MacArthur Fellow Lisa Parks charts the shift in critical focus from the potential of social media platforms to unite people around progressive causes to the need for “content moderation,” the practice of cleaning up digital pollution. Parks centers her analysis on The Cleaners (2018), Moritz Riesewieck and Hans Block's provocative documentary that delves into the lives and worlds of commercial content moderators at an unnamed company in the Philippines. The film's account of these digital-labor conditions prompts Parks' critical reflection on a series of issues: the delegation of U.S. media regulation to globally outsourced workers, the problematic trope of “cleaning,” the business of historical sanitization, and the black-boxing of infrastructural information.
Parks, Lisa D., and Delon W. Barfuss. Transepithelial transport and metabolism of glycine in S1, S2, and S3 cell types of the rabbit proximal tubule. Am J Physiol Renal Physiol 283: F1208-F1215, 2002 10.1152/ajprenal.00021.2002In the first of two sets of experiments, the lumen-to-cell and cell-to-bath transport rates for glycine were measured in the isolated-perfused medullary pars recta (S3 cells) of the rabbit proximal tubule at multiple luminal glycine concentrations (0-2.0 mM). The lumen-to-cell transport of glycine was saturated, which permitted the calculation of the transport maximum of disappearance rate of glycine from the lumen (pmol⅐min Ϫ1 ⅐mm tubular length Ϫ1), Km (mM), and paracellular leak (pmol⅐min Ϫ1 ⅐ mm tubular length Ϫ1 ⅐mM Ϫ1) values for this transport mechanism; these values were 4.3, 0.3, and 0.03, respectively. The cell-to-bath transport did not saturate but showed a linear relationship to cellular glycine concentration, 0.58 pmol⅐min Ϫ1 ⅐ mm tubular length Ϫ1 ⅐mM Ϫ1. The second set of experiments characterized the transport rate, cellular accumulation, and metabolic rate of lumen-to-cell transported [ 3 H]glycine in all segments (cell types) of the proximal tubule, pars convoluta (S1 cells), cortical pars recta (S2 cells), and medullary pars recta (S3 cells). These proximal tubular segments were isolated and perfused at a single glycine concentration of 11.2 M. From the results of this study and previous work (Barfuss DW and Schafer JA. Am J Physiol 236: F149-F162, 1979), we conclude that the axial heterogeneity for glycine lumen-to-cell and cell-to-bath transport capacity extends to the medullary pars recta (S3 cells; S1 Ͼ S2 Ͻ S3 for lumen-to-cell transport and S1 Ͼ S2 Ͼ S3 for cell-to-bath transport). Also, we conclude that lumen-to-cell transported glycine can be metabolized and its metabolic rate displays axial heterogeneity (S1 Ͼ S2 Ͼ S3). The physiological significances of these transport and metabolic characteristics of the S3 cell type permits the medullary pars recta to effectively recover glycine from very low luminal glycine concentrations and makes glycine available for protective and maintenance metabolism of the medullary pars recta. kidney; glutathione; nephron MUCH IS KNOWN ABOUT THE CHARACTERISTICS of amino acid transport in the epithelial cells of the proximal tubule as determined by several techniques, including whole animal studies, isolated tubule perfusion, microperfusion, cell culture, and membrane vesicle preparations (1,2,10,14,18,25). These studies were primarily focused on the transport of the luminal membrane, lumen-to-cell transport. In most of these studies, it is not apparent which of the proximal tubular cell types (S1, S2, or S3) were studied and the metabolic fate of the transported glycine was not determined.There are two sources of amino acids that are presented to the luminal membrane of the proximal tubule for transport. The first and largest amount is from filtration of blood at the glomerulus, and the second source is the result of digestion of f...
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