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Blood, 15 January 2006, Vol. 107, No. 2, pp. 661-668. Prepublished online as a Blood First Edition Paper on October 4, 2005; DOI 10.1182/blood-2005-03-1186. This Article Full Text (PDF) All Versions of this Article: 2005-03-1186v1 107/2/661    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Arimura, A. Articles by Batuman, V. Search for Related Content PubMed PubMed Citation Articles by Arimura, A. Articles by Batuman, V. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 29, 2005 Accepted July 29, 2005 Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury Akira Arimura*, Min Li, and Vecihi Batuman US-Japan Biomedical Research Laboratories, Tulane University F. Edward Hebert Research Center, New Orleans, LA, USA; Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA * Corresponding author; email: arimura{at}tulane.edu. The most common type of renal injury in multiple myeloma is chronic tubulointerstitial nephropathy associated with casts in tubule lumens, an entity referred to as "myeloma kidney" that often progresses to end stage kidney diseases. Myeloma kidney is associated with a significant increase in all-cause mortality, yet no effective intervention, except a limited use of steroid, is available. Here, we report that PACAP38 dramatically prevents injury of cultured renal proximal tubule cells caused by myeloma light chains through suppression of proinflammatory cytokines production, by inhibiting p38 MAPK and translocation of NFB via both PAC1- and VPAC1-receptors. The suppressive effects of PACAP was as effective as dexamethasone in all of their cytokine assays, and demonstrated both in vitro and in vivo. Furthermore, PACAP38 inhibits myeloma cell growth directly and may also indirectly by suppressing production of the growth factor, IL-6, from bone marrow stromal cells, that is stimulated by adhesion of myeloma cells. These findings render PACAP38 worth evaluation as a promising candidate for an effective and safe renoprotectant in myeloma kidney, and possibly other nephropathy, and also as a new antitumor agent in multiple myeloma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A new twist in myeloma treatment Paul W. Sanders Blood 2006 107: 413-414. [Full Text] [PDF] This article has been cited by other articles: M. Li, K. S. Hering-Smith, E. E. Simon, and V. Batuman Myeloma light chains induce epithelial-mesenchymal transition in human renal proximal tubule epithelial cells Nephrol. Dial. Transplant., March 1, 2008; 23(3): 860 - 870. [Abstract] [Full Text] [PDF] M. Hautmann, U. G. Friis, M. Desch, V. Todorov, H. Castrop, F. Segerer, C. Otto, G. Schutz, and F. Schweda Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Renin Secretion via Activation of PAC1 Receptors J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1150 - 1156. [Abstract] [Full Text] [PDF] P.-X. Wang and P. W. Sanders Immunoglobulin Light Chains Generate Hydrogen Peroxide J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1239 - 1245. [Abstract] [Full Text] [PDF] M. Li, S. Cortez, T. Nakamachi, V. Batuman, and A. Arimura Pituitary Adenylate Cyclase-Activating Polypeptide Is a Potent Inhibitor of the Growth of Light Chain-Secreting Human Multiple Myeloma Cells. Cancer Res., September 1, 2006; 66(17): 8796 - 8803. [Abstract] [Full Text] [PDF]

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