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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/F534    most recent 00408.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lee, Y. J. Articles by Han, H. J. Search for Related Content PubMed PubMed Citation Articles by Lee, Y. J. Articles by Han, H. J.

Albumin-stimulated DNA synthesis is mediated by Ca²⁺/PKC as well as EGF receptor-dependent p44/42 MAPK and NF-B signal pathways in renal proximal tubule cells

Department of Veterinary Physiology, Biotherapy Human Resources Center (BK21), College of Veterinary Medicine, Chonnam National University, Gwangju, Korea

Submitted 3 September 2007 ; accepted in final form 21 December 2007

It is now recognized that significant tubular reabsorption of albumin occurs under physiological conditions that may play an important role in maintaining proximal tubular integrity and function. Therefore, this study examined the effect of bovine serum albumin (BSA) on DNA synthesis and its related signal molecules in primary cultured rabbit renal proximal tubule cells (PTCs). BSA increased the level of [³H]thymidine incorporation in a dose (3 mg/ml)- and time (3 h)-dependent manner, intracellular Ca²⁺ concentration, and the level of protein kinase C (PKC) phosphorylation and stimulated the phosphorylation of the epidermal growth factor receptor (EGFR), which was inhibited by EGTA (extracellular Ca²⁺ chelator), 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM, intracellular Ca²⁺ chelator), or PKC inhibitors (staurosporine or bisindolylmaleimide I). In addition, the PKC inhibitors or an EGFR inhibitor (AG-1478) blocked the BSA-induced phosphorylation of p44/42 mitogen-activated protein kinases (MAPKs). BSA also increased the level of nuclear factor-B (NF-B) and inhibitor of NF-B (IB) phosphorylation, which was blocked by staurosporine, AG-1478, or PD-98059 (p44/42 MAPK inhibitor). Inhibition of Ca²⁺, PKC, EGFR, p44/42 MAPK, or NF-B signal pathways blocked the BSA-induced incorporation of [³H]thymidine. Consequently, the inhibition of Ca²⁺, PKC, EGFR, p44/42 MAPKs, or NF-B blocked the BSA-induced increases in cyclin D1, cyclin-dependent kinase (CDK)4, cyclin E, or CDK2 and restored the BSA-induced inhibition of p21^WAF/Cip1 and p27^Kip1 expression. In conclusion, BSA stimulates DNA synthesis that is mediated by Ca²⁺/PKC as well as the EGFR-dependent p44/42 MAPK and NF-B signal pathways in PTCs.

kidney; cyclins; cyclin-dependent kinases; p21^WAF/Cip1; p27^Kip1