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- Title
Albumin stimulates cell growth, l-arginine transport, and metabolism to polyamines in human proximal tubular cells.
- Authors
Ashman, Neil; Harwood, Steven M.; Kieswich, Julius; Allen, David A.; Roberts, Norman B.; Mendes-Ribeiro, A. Claudio; Yaqoob, Muhammad M.
- Abstract
Albumin stimulates cell growth, L-arginine transport, and metabolism to polyamines in human proximal tubular cells. Background. Pure albumin stimulates proximal tubular epithelial cell (PTEC) proliferation, and may have a role in homeostasis in health, as well as in disrupted PTEC turnover in proteinuric nephropathies. We investigated a role for arginine and its metabolites, the polyamines, in this process, given the ability of polyamines to trigger proliferation in other mammalian cells. Methods.[3H]-L-arginine uptake was examined after incubation with 20 mg/mL recombinant human serum albumin (rHSA) in HK-2 PTEC monolayers. Nitric oxide synthase (NOS) and arginase activity was measured; NOS, arginase, and ornithine decarboxylase (ODC) expression was identified by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Polyamine synthesis and intracellular amino acid concentrations were compared using high-performance liquid chromatography, and cell growth measured by[3H]-thymidine incorporation. Results. In HK-2 PTEC exposed to 20 mg/mL rHSA for 24 hours, cell proliferation as determined by[3H]-thymidine incorporation was increased. In parallel, L-arginine transport capacity was increased in a dose- and time-dependent manner. This effect was specific to rHSA, and was not seen with transferrin or immunoglobulin G. The intracellular concentration of L-arginine remained unchanged, although L-ornithine was increased with rHSA incubation. rHSA up-regulated type II arginase mRNA, and increased arginase activity, although no difference in nitric oxide synthase expression or activity was seen. ODC mRNA was increased, as were intracellular polyamine concentrations.α-Difluoromethylornithine (DFMO), an ODC inhibitor, reduced intracellular polyamine concentrations and rHSA-induced cell proliferation to control levels. Conclusion. The arginine-ornithine-polyamine pathway appears enhanced in PTEC incubated with rHSA and is involved in cellular proliferation; this may offer novel approaches to understanding progressive proteinuric nephropathies.
- Subjects
ALBUMINS; ARGININE; POLYAMINES; KIDNEY tubules; EPITHELIAL cells; CELL proliferation; RNA metabolism; AMINO acid metabolism; ARGININE metabolism; HOMEOSTASIS; BIOCHEMISTRY; RESEARCH; EFLORNITHINE; BIOLOGICAL transport; RESEARCH methodology; RNA; MEDICAL cooperation; EVALUATION research; SERUM albumin; AMINES; NUCLEOTIDES; PHENOMENOLOGY; HYDROLASES; CELL division; GENE expression; COMPARATIVE studies; ENZYMES; OXIDOREDUCTASES; CELL lines; RECOMBINANT proteins; ENZYME inhibitors; PHARMACODYNAMICS
- Publication
Kidney International, 2005, Vol 67, Issue 5, p1878
- ISSN
0085-2538
- Publication type
journal article
- DOI
10.1111/j.1523-1755.2005.00286.x