Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
Add more filters










Publication year range
1.
Buenos Aires; Medica Panamericana; 7º ed; 2011. XXI, 441 p. tab, graf.
Monography in Spanish | LILACS | ID: biblio-983594

ABSTRACT

Tratada de la fisiología del cuerpo humano, sus sistemas y aparatos y los numerosos procesos que los mantienen en funcionamiento.


Subject(s)
Male , Female , Cell Physiological Phenomena , Physiology
2.
Buenos Aires; Médica Panamericana; 7 ed; 2009. XIII, 441 p. tab, graf.
Monography in Spanish | LILACS | ID: biblio-983589

ABSTRACT

Oferece una visión general acerca de la fisiología, el cuerpo, sus sistemas y aparatos, y los numerosos procesos que los mantienen en funcionamiento. Su interrelación con la fisiopatología y la medicina interna.


Subject(s)
Physiology
3.
Am J Physiol Renal Physiol ; 293(1): F382-90, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17429029

ABSTRACT

D-Serine selectively causes necrosis of S(3) segments of proximal tubules in rats. This leads to aminoaciduria and glucosuria. Coinjection of the nonmetabolizable amino acid alpha-aminoisobutyric acid (AIB) prevents the tubulopathy. D-serine is selectively reabsorbed in S(3), thereby gaining access to peroxisomal D-amino acid oxidase (D-AAO). D-AAO-mediated metabolism produces reactive oxygen species. We determined the fractional excretion of amino acids and glucose in rats after intraperitoneal injection of d-serine alone or together with reduced glutathione (GSH) or AIB. Both compounds prevented the hyperaminoaciduria. We measured GSH concentrations in renal tissue before (control) and after D-serine injection and found that GSH levels decreased to approximately 30% of control. This decrease was prevented when equimolar GSH was coinjected with D-serine. To find out why AIB protected the tubule from D-serine toxicity, we microinfused D-[(14)C]serine or [(14)C]AIB (0.36 mmol/l) together with [(3)H]inulin in late proximal tubules in vivo and measured the radioactivity in the final urine. Fractional reabsorption of D-[(14)C]serine and [(14)C]AIB amounted to 55 and 70%, respectively, and 80 mmol/l of AIB or D-serine mutually prevented reabsorption to a great extent. D-AAO activity measured in vitro (using D-serine as substrate) was not influenced by a 10-fold higher AIB concentration. We conclude from these results that 1) D-AAO-mediated d-serine metabolism lowers renal GSH concentrations and thereby provokes tubular damage because reduction of reactive oxygen species by GSH is diminished and 2) AIB prevents d-serine-induced tubulopathy by inhibition of D-serine uptake in S(3) segments rather than by interfering with intracellular D-AAO-mediated D-serine metabolism.


Subject(s)
Aminoisobutyric Acids/therapeutic use , Kidney Diseases/chemically induced , Kidney Diseases/prevention & control , Serine/toxicity , Amino Acids/blood , Animals , D-Amino-Acid Oxidase/antagonists & inhibitors , Dose-Response Relationship, Drug , Glucose/metabolism , Glutathione/metabolism , Glycosuria/chemically induced , Hydrogen Peroxide/metabolism , Injections, Intraperitoneal , Insulin , Kidney/drug effects , Kidney/metabolism , Kidney Diseases/pathology , Kidney Tubules, Proximal/cytology , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/metabolism , Loop of Henle/drug effects , Loop of Henle/metabolism , Male , Oxidation-Reduction , Rats , Rats, Wistar , Serine/administration & dosage , Serine/metabolism
4.
Cell Physiol Biochem ; 14(1-2): 47-56, 2004.
Article in English | MEDLINE | ID: mdl-14976406

ABSTRACT

Ochratoxin A (OTA) is a potent nephrotoxin and suspected to be involved in the etiology of Balkan endemic nephropathy. Nanomolar concentrations of this mycotoxin induce apoptosis in renal collecting duct-derived cells (MDCK-C7 cells, resembling principal cells). We studied the role of mitochondria in this process by inhibition of the mitochondrial respiratory chain, the F1FO-ATP synthase or by uncoupling. Also, the role of intra- and extracellular pH in apoptosis induction was investigated. Activation of caspase-3 and DNA ladder formation were used to monitor the apoptotic response. When cells were incubated with inhibitors of the mitochondrial respiratory chain or an inhibitor of the ATP-synthase, OTA-induced apoptosis was enhanced dramatically. Also, mitochondrial uncoupling potentiated the effects of OTA. OTA-induced apoptosis was not dependent on a decrease of the mitochondrial potential. Mitochondrial blockade led to medium acidification due to enhanced production of lactic acid. Artificial extracellular acidification potentiated OTA-induced caspase-3 activation. Artificial extracellular alkalization had no influence on caspase-3 activity. Intracellular pH after 24 hours exposure to inhibitors of mitochondria or acidic or alkaline media did not correlate with caspase-3 activity but correlated with caspase-3 activity when OTA was present: acidic intracellular pH (pHin) was associated with higher caspase-3 activity as compared to alkaline pHin. We conclude that extra- and intracellular pH are important factors in OTA-induced apoptosis in MDCK-C7 cells. The physiologically changing pH conditions in the collecting duct can thus alter or even aggravate the toxic effects of OTA.


Subject(s)
Apoptosis/physiology , Kidney Tubules, Collecting/drug effects , Kidney Tubules, Collecting/metabolism , Mitochondria/physiology , Ochratoxins/toxicity , Acids/pharmacology , Alkalies/pharmacology , Animals , Apoptosis/drug effects , Caspase 3 , Caspases/metabolism , Cell Line , Clone Cells/drug effects , Clone Cells/metabolism , DNA/metabolism , Dogs , Hydrogen-Ion Concentration/drug effects , Kidney Tubules, Collecting/cytology , Lactic Acid/metabolism , Mitochondria/drug effects , Uncoupling Agents/pharmacology
5.
Am J Physiol Renal Physiol ; 284(6): F1181-9, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12736166

ABSTRACT

Filtered myo-inositol, an important renal intracellular organic osmolyte, is almost completely reabsorbed. To examine tubule sites and specificity and, thus possible mechanism of this reabsorption, we microinfused myo-[(3)H]inositol or D-[(3)H]glucose into early proximal (EP), late proximal (LP), or early distal tubule sections of superficial nephrons and into long loops of Henle (LLH) of juxtamedullary nephrons and papillary vasa recta in rats in vivo et situ and determined urinary fractional recovery of the (3)H label compared with comicroinfused [(14)C]inulin. To determine the extent to which the proximal convoluted tubule (PCT) alone contributes to myo-inositol reabsorption, we also microperfused this tubule segment between EP and LP puncture sites. We examined specificity of reabsorptive carrier(s) by adding high concentrations of other polyols and monosaccharides to the infusate. The results show that >60% of the physiological glomerular load of myo-inositol can be reabsorbed in the PCT and >90% in the short loop of Henle (SLH) by a saturable, phloridzin-sensitive process. myo-Inositol can also be reabsorbed in the ascending limb of LLH and can move from papillary vasa recta blood into ipsilateral tubular structures. Essentially no reabsorption occurred in nephron segments beyond the SLH or in collecting ducts. Specificity studies indicate that reabsorption probably occurs via a luminal Na(+)-myo-inositol cotransporter.


Subject(s)
Glucose/metabolism , Inositol/metabolism , Kidney Tubules/metabolism , Kidney/metabolism , Absorption , Animals , Biological Transport, Active , Carrier Proteins/metabolism , Functional Laterality/physiology , Hydrogen-Ion Concentration , Inulin/urine , Kidney/drug effects , Kidney Tubules/drug effects , Kidney Tubules, Distal/drug effects , Kidney Tubules, Distal/metabolism , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/metabolism , Kinetics , Loop of Henle/drug effects , Loop of Henle/metabolism , Male , Nephrons/drug effects , Nephrons/metabolism , Phlorhizin/pharmacology , Rats , Rats, Wistar
6.
Kidney Int ; 63(5): 1725-35, 2003 May.
Article in English | MEDLINE | ID: mdl-12675848

ABSTRACT

BACKGROUND: Nephrotoxic substances like cisplatin or ochratoxin A (OTA) induce cell death in human proximal tubule-derived cells (IHKE cells). Mitochondria play a significant role in apoptosis and loss of their function may influence OTA- or cisplatin-induced apoptosis. Extracellular pH also plays an important role in tumor genesis. Therefore, we investigated the role of mitochondria and intra- and extracellular pH on cell death induction by cisplatin or OTA. METHODS: IHKE cells were incubated in the presence of OTA or cisplatin, together with inhibitors of the mitochondrial metabolism, and the activity of caspase-3 was measured and DNA laddering was monitored. Adenosine triphosphate (ATP) content of the cells, lactate release into the media, and glucose consumption was determined. In addition, media and cells were acidified or alkalized artificially to investigate the effect of intra- and extracellular pH on cell death induction. Cytochrome C was immunodetected in cellular compartments. RESULTS: Inhibition of the mitochondrial function reduced OTA- or cisplatin-induced cell death and led to considerable lactic acid production and extracellular acidification. Intra- and extracellular acidification prevented cells from cell death induced by OTA or cisplatin. No cytochrome C release from mitochondria could be detected during 24 hours of exposure to OTA or cisplatin. CONCLUSION: We conclude that OTA- or cisplatin-induced cell death is dependent on functional and intact, ATP-producing mitochondria and that intra- and extracellular pH is crucial for induction of cell death in IHKE cells.


Subject(s)
Acidosis/pathology , Apoptosis/physiology , Epithelial Cells/cytology , Kidney Tubules, Proximal/cytology , Mitochondria/physiology , Acidosis/metabolism , Adenosine Triphosphate/metabolism , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Buffers , Carcinogens/pharmacology , Caspase 3 , Caspases/metabolism , Cell Line, Transformed , Cisplatin/pharmacology , Cytochromes c/metabolism , DNA/analysis , Electron Transport/drug effects , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Extracellular Space/metabolism , Glucose/metabolism , Humans , Hydrogen-Ion Concentration , Lactic Acid/metabolism , Mitochondria/drug effects , Mitochondrial ADP, ATP Translocases/antagonists & inhibitors , Mitochondrial Proton-Translocating ATPases/antagonists & inhibitors , Ochratoxins/pharmacology , Uncoupling Agents/pharmacology
7.
Steroids ; 67(6): 499-504, 2002 May.
Article in English | MEDLINE | ID: mdl-11960627

ABSTRACT

It has been suggested that steroids interact with peptide hormones in part by rapid, potentially non-genomic, mechanisms. The peptide hormone epidermal growth factor (EGF) regulates cell proliferation and ion transport using ERK1/2 as downstream signal. Furthermore, the EGF-receptor (EGF-R) is involved in signaling by G-protein-coupled receptors, growth hormone and cytokines via transactivation. We show that aldosterone modulates Na(+)/H(+)-exchange in renal collecting duct-derived Madin-Darby canine kidney (MDCK) cells via ERK1/2 in a similar way as compared to growth factors. Furthermore, we tested the hypothesis that aldosterone uses the EGF-R as heterologous signal transducer in MDCK cells. Aldosterone induces a rapid increase of ERK1/2 phosphorylation and cytosolic Ca(2+)-concentration of similar extend as compared to EGF. Furthermore, aldosterone stimulates EGF-R Tyr-phosphorylation. Inhibition of EGF-R kinase abolished aldosterone-induced signaling. Aldosterone-induced Ca(2+)-influx seems to be mediated by the activation of ERK1/2, whereas ERK1/2 activation does not depend on Ca(2+)-influx. Our data show that aldosterone uses the EGF-R-ERK1/2 signaling cascade to elicit its rapid effects in MDCK cells.


Subject(s)
Aldosterone/pharmacology , Calcium/metabolism , ErbB Receptors/metabolism , Kidney/cytology , Signal Transduction/drug effects , Animals , Cells, Cultured , Dogs , Epithelium/drug effects , Epithelium/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation/drug effects , Signal Transduction/physiology , Sodium-Hydrogen Exchangers/drug effects , Sodium-Hydrogen Exchangers/metabolism
8.
Am J Physiol Renal Physiol ; 282(4): F669-79, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11880328

ABSTRACT

Epidermal growth factor (EGF) regulates cell proliferation, differentiation, and ion transport by using extracellular signal-regulated kinase (ERK)1/2 as a downstream signal. Furthermore, the EGF-receptor (EGF-R) is involved in signaling by G protein-coupled receptors, growth hormone, and cytokines by means of transactivation. It has been suggested that steroids interact with peptide hormones, in part, by rapid, potentially nongenomic, mechanisms. Previously, we have shown that aldosterone modulates Na(+)/H(+) exchange in Madin-Darby canine kidney (MDCK) cells by means of ERK1/2 in a way similar to growth factors. Here, we tested the hypothesis that aldosterone uses the EGF-R as a heterologous signal transducer in MDCK cells. Nanomolar concentrations of aldosterone induce a rapid increase in ERK1/2 phosphorylation, cellular Ca(2+) concentration, and Na(+)/H(+) exchange activity similar to increases induced by EGF. Furthermore, aldosterone induced a rapid increase in EGF-R-Tyr phosphorylation, and inhibition of EGF-R kinase abolished aldosterone-induced signaling. Inhibition of ERK1/2 phosphorylation reduced the Ca(2+) response, whereas prevention of Ca(2+) influx did not abolish ERK1/2 phosphorylation. Our data show that aldosterone uses the EGF-R-ERK1/2 signaling cascade to elicit its rapid effects in MDCK cells.


Subject(s)
Aldosterone/pharmacology , ErbB Receptors/drug effects , Signal Transduction/drug effects , Animals , Arachidonic Acid/metabolism , Blotting, Western , Calcium/metabolism , Cell Division/drug effects , Cell Line , Cell Membrane/drug effects , Cytosol/drug effects , Cytosol/metabolism , Dogs , Enzyme-Linked Immunosorbent Assay , GTP-Binding Proteins/metabolism , Hydrogen-Ion Concentration , Inositol 1,4,5-Trisphosphate/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation , Precipitin Tests
SELECTION OF CITATIONS
SEARCH DETAIL
...