PMID- 10677388 OWN - NLM STAT- MEDLINE DCOM- 20000411 LR - 20180815 IS - 0143-5221 (Print) IS - 0143-5221 (Linking) VI - 98 IP - 3 DP - 2000 Mar TI - Albumin stimulates p44/p42 extracellular-signal-regulated mitogen-activated protein kinase in opossum kidney proximal tubular cells. PG - 295-301 AB - The presence of protein in the urine of patients with renal disease is an adverse prognostic feature. It has therefore been suggested that proteinuria per se may be responsible for the development of renal tubulo-interstitial scarring and fibrosis, and disturbances in tubular cell growth and proliferation. We have used the opossum kidney proximal tubular cell line to investigate the effects of albumin on cell growth. The effect of albumin on cell proliferation was investigated by cell counting and measurement of [(3)H]thymidine incorporation. We studied the effect of recombinant human albumin on the activity of p44/p42 extracellular-signal-regulated mitogen-activated protein kinase (MAP kinase ) using an in vitro kinase assay, and immunoblotting with antibodies against active extracellular-signal-regulated kinase (ERK). The effects of the ERK inhibitor PD98059 were also examined. Recombinant human albumin was found to stimulate proliferation of opossum kidney cells in a dose-dependent manner, with maximal stimulation at a concentration of 1 mg/ml. In addition, recombinant human albumin activated ERK in a time-dependent (maximal after 5 min) and dose-dependent (maximal at 1 mg/ml) fashion. These effects on cell proliferation and ERK activity were inhibited by PD98059, and were not reproduced by ovalbumin or mannitol. The data therefore indicate that albumin is able to stimulate growth and proliferation of proximal tubular cells that is dependent on the ERK family of MAP kinases. The potential importance of this pathway in the development of renal disease is discussed. FAU - Dixon, R AU - Dixon R AD - Department of Cell Physiology and Pharmacology, Leicester University School of Medicine, P.O. Box 138, Maurice Shock Medical Sciences Building, University Road, Leicester LE1 9HN, UK. FAU - Brunskill, N J AU - Brunskill NJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Clin Sci (Lond) JT - Clinical science (London, England : 1979) JID - 7905731 RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 0 (Recombinant Proteins) RN - 0 (Serum Albumin) RN - 3OWL53L36A (Mannitol) RN - 9006-59-1 (Ovalbumin) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) RN - VC2W18DGKR (Thymidine) SB - IM MH - Animals MH - Cell Count MH - Cell Division/drug effects MH - Cell Line MH - Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Flavonoids/pharmacology MH - Humans MH - Kidney Tubules, Proximal/*drug effects/enzymology/pathology MH - Mannitol/pharmacology MH - Mitogen-Activated Protein Kinase 1/*metabolism MH - Mitogen-Activated Protein Kinases/analysis/antagonists & inhibitors/metabolism MH - Opossums MH - Ovalbumin/pharmacology MH - Recombinant Proteins/pharmacology MH - Serum Albumin/*pharmacology MH - Thymidine/metabolism EDAT- 2000/03/24 09:00 MHDA- 2000/04/15 09:00 CRDT- 2000/03/24 09:00 PHST- 2000/03/24 09:00 [pubmed] PHST- 2000/04/15 09:00 [medline] PHST- 2000/03/24 09:00 [entrez] PST - ppublish SO - Clin Sci (Lond). 2000 Mar;98(3):295-301.