Overload of reactive oxygen species during diabetes is known to impair cellular homeostasis and to promote deterioration of membrane function in the organism. The aim of the present study was to examine the effect of dietary supplementation with the pyridoindole atioxidant stobadine on functional properties of the renal Na, K-ATPase in diabetic rats. After 16 weeks of streptozotocin-induced diabetes (single intravenous dose of streptozotocin; 55 mg/kg), a significant inhibition (by 35%-42%) of the enzyme was observed throughout the range of NaCl 2-100 mmol/l, probably as an event of altered functional properties of Na,K-ATPase, suggested by the 42% decrease of the V(max) value. Administration of 0.05% (w/w) stobadine in the diet dramatically improved the function of renal Na,K-ATPase in diabetic rats with regard to sodium handling, as suggested by significant stimulation (by 104%-77% in accordance with increasing concentration of NaCl) of the enzyme over the whole NaCl concentration range investigated. This stimulatory effect was accompanied by an increase of V(max) value to the level of nondiabetic rats on standard diet. In conclusion, stobadine was found to antagonise the negative effects of diabetes on the renal Na,K-ATPase, preserving its normal function in regulation of intracellular homeostasis of Na(+) and K(+) ions.
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http://dx.doi.org/10.1007/s00592-004-0162-y | DOI Listing |
Life Sci
February 2020
Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC, United States of America. Electronic address:
Hypertension is a risk factor for premature death and roughly 50% of hypertensive patients are salt-sensitive. The incidence of salt-sensitive hypertension increases with age. However, the mechanisms of salt-sensitive hypertension are not well understood.
View Article and Find Full Text PDFBiochim Biophys Acta
November 2016
Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC, USA. Electronic address:
Our laboratory has recently demonstrated that low concentrations of ouabain increase blood pressure in rats associated with stimulation of NaK ATPase activity and activation of the Src signaling cascade in NHE1-dependent manner. Proteomic analysis of human kidney proximal tubule cells (HKC11) suggested that the Angiotensin II type 1 receptor (AT1R) as an ouabain-associating protein. We hypothesize that ouabain-induced stimulation of NaK ATPase activity is mediated through AT1R.
View Article and Find Full Text PDFJ Biol Chem
November 2013
Department of Pharmacology, Physiology and Toxicology, JCE School of Medicine at Marshall University, Huntington, West Virginia 25755. Electronic address:
Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate sodium reabsorption in the renal proximal tubule. We report here that reactive oxygen species are required to initiate ouabain-stimulated Na/K-ATPase·c-Src signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented ouabain-stimulated Na/K-ATPase·c-Src signaling, protein carbonylation, redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and inhibition of active transepithelial (22)Na(+) transport.
View Article and Find Full Text PDFJ Am Soc Nephrol
June 2004
Department of Pediatrics, Yale University, New Haven, CT 06520-8064, USA.
To test a putative cause and effect relationship between heat-shock protein (HSP) expression and response to renal cell injury, HSP72 and HSP25 were differentially inhibited in LLC-PK1 cells by means of transcription factor decoy and short interference RNA (siRNA). Cellular injury was assessed by solubilization of NaK ATPase (S-NaK). An exonuclease-resistant, ethylene glycol-bridged, circular oligonucleotide decoy for heat-shock transcription factor (HSF)-1, based on the sequence of the porcine heat-shock element, was constructed and validated.
View Article and Find Full Text PDFMinerva Urol Nefrol
December 2002
Department of Medicine, Mount Sinai School of Medicine, Box 1243, 1425 Madison Avenue, New York, NY 10029, USA.
Genetically based polycystic kidney diseases include autosomal dominant (ADPKD) and recessive (ARPKD) polycystic kidney diseases, nephronophthisis and medullary cystic disease. The PKD1 and PKD2 genes responsible for ADPKD and their respective encoded proteins polycystin-1 and polycystin-2 are under intense study and clues are developing as to their function and roles in the disease process. Structure-function analysis suggests that polycystins form multiprotein complexes with focal adhesion and cell-cell adherens junction proteins, which then initiate intracellular signaling events culminating in regulation of transcription of genes controlling proliferation and differentiation.
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