Abstract

Our aims during this grant period will be to delineate further the signals, effectors, pathways and rate-limiting biochemical steps for both the acute and adaptive changes in renal ammoniagenesis in response to alterations in H+ and K+ homeostasis. In addition the mechanisms of action of several modulators of ammoniagenesis will be explored, including prostaglandins, calcium, cyclic AMP, glucocorticoids and aldosterone. The major experimental model utilized will be renal epithelium grown in cell culture. The LLC-PK1 continuous pig cell line will be used. In addition primary cultures of rat, dog and human proximal tubular epithelium will be developed and utilized. Techniques employed with cultured cells will include enzyme analysis, measurments of metabolites, pulse chase isotopic studies, investigation of isolated mitochondria, and studies of the molecular biology of adaptation. In addition to cell culture, experiments with intact animals, isolated perfused kidney, renal cortical tubule and isolated mitochondria will be used to address the mechanisms of decreased NH3 production with acute alkalosis, the signal for adaptation to chronic acidosis, the inhibitory effect of PGF2alpha and the K+ sparing effect of increased NH3 production.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK025248-16
Application #
3483438
Study Section
Special Emphasis Panel (NSS)
Project Start
1988-09-01
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
16
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089

  Publications

Sahai, A; Mei, C; Schrier, R W et al. (1999) Mechanisms of chronic hypoxia-induced renal cell growth. Kidney Int 56:1277-81
Hood, V L; Tannen, R L (1998) Protection of acid-base balance by pH regulation of acid production. N Engl J Med 339:819-26
Sahai, A; Mei, C; Zavosh, A et al. (1997) Chronic hypoxia induces LLC-PK1 cell proliferation and dedifferentiation by the activation of protein kinase C. Am J Physiol 272:F809-15
Sahai, A; Mei, C; Pattison, T A et al. (1997) Chronic hypoxia induces proliferation of cultured mesangial cells: role of calcium and protein kinase C. Am J Physiol 273:F954-60
Tannen, R L; Nissim, I; Sahi, A (1996) Hormonal mediators of ammoniagenesis: mechanism of action of PGF2 alpha and the implications for other hormones. Kidney Int 50:15-25
Sahai, A; Nissim, I; Sandler, R S et al. (1995) Prostaglandin F2 alpha- and 12-O-tetradecanoylphorbol-13-acetate-induced alterations in the pathways of renal ammoniagenesis. J Am Soc Nephrol 5:1792-8
Sahai, A; Patel, M S; Zavosh, A S et al. (1994) Chronic hypoxia impairs the differentiation of 3T3-L1 fibroblast in culture: role of sustained protein kinase C activation. J Cell Physiol 160:107-12
Nissim, I; Sahai, A; Sandler, R S et al. (1994) The intensity of acidosis differentially alters the pathways of ammoniagenesis in LLC-PK1 cells. Kidney Int 45:1014-9
Tannen, R L; Sahai, A (1994) Hypoxia impairs cellular differentiation. Trans Am Clin Climatol Assoc 105:111-7;discussion 118-9
Tang, M J; Tannen, R L (1994) Metabolic substrates alter attachment and differentiated functions of proximal tubule cell culture. J Am Soc Nephrol 4:1908-11

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