HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/1/G117    most recent 00397.2005v1 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 HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Kiang, J. G. Articles by Tsokos, G. C. Search for Related Content PubMed PubMed Citation Articles by Kiang, J. G. Articles by Tsokos, G. C.

MUCOSAL BIOLOGY

Geldanamycin prevents hemorrhage-induced ATP loss by overexpressing inducible HSP70 and activating pyruvate dehydrogenase

¹Walter Reed Army Institute of Research, Silver Spring; Departments of ²Medicine and of ³Pharmacology, Uniformed Services University of The Health Sciences, Bethesda, Maryland; and ⁴United States Army Institute of Surgical Research, San Antonio, Texas

Submitted 25 August 2005 ; accepted in final form 15 March 2006

Hemorrhage in mice results in decreased ATP levels in the jejunum, lung, kidney, heart, and brain but not in liver tissue lysates, albeit at variable levels and time kinetics. The decreased protein expression and activity of pyruvate dehydrogenase (PDH) accounted for the hemorrhage-induced ATP loss. Treatment with geldanamycin (GA; 1 µg/g body wt), a known inducer of heat shock protein (HSP)70, inhibited the hemorrhage-induced ATP loss in the jejunum, lung, heart, kidney, and brain. GA was found to increase PDH protein, preserve PDH enzymatic activity, and inhibit mucosal injury in jejunum tissues. GA-induced HSP70i was found to form complexes with PDH protein. HSP70 gene transfer into intestinal epithelial cells promoted PDH and ATP levels, whereas HSP70 short interfering RNA limited them. We conclude that agents able to increase the expression of HSP70 and PDH may be of value in reducing pathology resulting from hemorrhage-associated ATP loss.

heat shock protein 70; intestine

This article has been cited by other articles:

				J. G. Kiang, P. D. Bowman, X. Lu, Y. Li, B. W. Wu, H. H. Loh, K. T. Tsen, and G. C. Tsokos Geldanamycin inhibits hemorrhage-induced increases in caspase-3 activity: role of inducible nitric oxide synthase J Appl Physiol, September 1, 2007; 103(3): 1045 - 1055. [Abstract] [Full Text] [PDF]

				J. G. Kiang, R. M. Peckham, L. E. Duke, T. Shimizu, I. H. Chaudry, and G. C. Tsokos Androstenediol inhibits the trauma-hemorrhage-induced increase in caspase-3 by downregulating the inducible nitric oxide synthase pathway J Appl Physiol, March 1, 2007; 102(3): 933 - 941. [Abstract] [Full Text] [PDF]