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Albumin stimulates cell growth, l-arginine transport, and metabolism to polyamines in human proximal tubular cells.
Kidney Int. 2005 May; 67(5):1878-89.KI

Abstract

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

[(3)H]-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 [(3)H]-thymidine incorporation.

RESULTS

In HK-2 PTEC exposed to 20 mg/mL rHSA for 24 hours, cell proliferation as determined by [(3)H]-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. alpha-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.

Authors+Show Affiliations

Department of Clinical Chemistry, University of Liverpool, Liverpool, United Kingdom. neil.ashman@bartsandthelondon.nhs.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15840035

Citation

Ashman, Neil, et al. "Albumin Stimulates Cell Growth, L-arginine Transport, and Metabolism to Polyamines in Human Proximal Tubular Cells." Kidney International, vol. 67, no. 5, 2005, pp. 1878-89.
Ashman N, Harwood SM, Kieswich J, et al. Albumin stimulates cell growth, l-arginine transport, and metabolism to polyamines in human proximal tubular cells. Kidney Int. 2005;67(5):1878-89.
Ashman, N., Harwood, S. M., Kieswich, J., Allen, D. A., Roberts, N. B., Mendes-Ribeiro, A. C., & Yaqoob, M. M. (2005). Albumin stimulates cell growth, l-arginine transport, and metabolism to polyamines in human proximal tubular cells. Kidney International, 67(5), 1878-89.
Ashman N, et al. Albumin Stimulates Cell Growth, L-arginine Transport, and Metabolism to Polyamines in Human Proximal Tubular Cells. Kidney Int. 2005;67(5):1878-89. PubMed PMID: 15840035.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Albumin stimulates cell growth, l-arginine transport, and metabolism to polyamines in human proximal tubular cells. AU - Ashman,Neil, AU - Harwood,Steven M, AU - Kieswich,Julius, AU - Allen,David A, AU - Roberts,Norman B, AU - Mendes-Ribeiro,A Claudio, AU - Yaqoob,Muhammad M, PY - 2005/4/21/pubmed PY - 2005/8/23/medline PY - 2005/4/21/entrez SP - 1878 EP - 89 JF - Kidney international JO - Kidney Int VL - 67 IS - 5 N2 - 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: [(3)H]-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 [(3)H]-thymidine incorporation. RESULTS: In HK-2 PTEC exposed to 20 mg/mL rHSA for 24 hours, cell proliferation as determined by [(3)H]-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. alpha-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. SN - 0085-2538 UR - https://www.unboundmedicine.com/medline/citation/15840035/Albumin_stimulates_cell_growth_l_arginine_transport_and_metabolism_to_polyamines_in_human_proximal_tubular_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(15)50666-2 DB - PRIME DP - Unbound Medicine ER -