This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Weinberg, J. M. Articles by Nissim, I. Search for Related Content PubMed PubMed Citation Articles by Weinberg, J. M. Articles by Nissim, I.

(American Journal of Pathology. 2001;158:2153-2164.)
© 2001 American Society for Investigative Pathology

Regular Article

Energetic Determinants of Tyrosine Phosphorylation of Focal Adhesion Proteins during Hypoxia/Reoxygenation of Kidney Proximal Tubules

Joel M. Weinberg^*, Manjeri A. Venkatachalam, Nancy F. Roeser^*, Ruth A. Senter^* and Itzhak Nissim

From the Department of Internal Medicine,^*
Division of Nephrology, University of Michigan and the Veteran’s Administration Medical Center, Ann Arbor, Michigan; the Departments of Pathology and Medicine,
The University of Texas Health Science Center at San Antonio, San Antonio, Texas; and the Division of Child Development,
Children’s Hospital of Philadelphia, and the Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Anaerobic mitochondrial metabolism of -ketoglutarate and aspartate or -ketoglutarate and malate can prevent and reverse severe mitochondrial dysfunction during reoxygenation after 60 minutes of hypoxia in kidney proximal tubules.³⁴ The present studies demonstrate that, during hypoxia, paxillin, focal adhesion kinase, and p130^cas migrated faster by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, their phosphotyrosine (pY) content decreased to 5% of that in oxygenated tubules without changes in total protein, and the normally basal immunostaining of ß1 and 6 integrin subunits, pY, and paxillin was lost or markedly decreased. During reoxygenation without supplemental substrates, recovery of pY and basal localization of the focal adhesion proteins was poor. -Ketoglutarate and aspartate, which maintained slightly higher levels of ATP during hypoxia, also maintained 2.5-fold higher levels of pY during this period, and promoted full recovery of pY content and basal localization of focal adhesion proteins during subsequent reoxygenation. Similarly complete recovery was made possible by provision of -ketoglutarate and aspartate or -ketoglutarate and malate only during reoxygenation. These data emphasize the importance of very low energy thresholds for maintaining the integrity of key structural and biochemical components required for cellular survival and reaffirm the value of approaches aimed at conserving or generating energy in cells injured by hypoxia or ischemia.

This article has been cited by other articles:

				T. Feldkamp, J. M. Weinberg, M. Horbelt, C. Von Kropff, O. Witzke, J. Nurnberger, and A. Kribben Evidence for involvement of nonesterified fatty acid-induced protonophoric uncoupling during mitochondrial dysfunction caused by hypoxia and reoxygenation Nephrol. Dial. Transplant., August 1, 2008; (2008) gfn436v1. [Abstract] [Full Text] [PDF]

				M. Alderliesten, M. de Graauw, J. Oldenampsen, Y. Qin, C. Pont, L. van Buren, and B. van de Water Extracellular Signal-Regulated Kinase Activation during Renal Ischemia/Reperfusion Mediates Focal Adhesion Dissolution and Renal Injury Am. J. Pathol., August 1, 2007; 171(2): 452 - 462. [Abstract] [Full Text] [PDF]

				T. Feldkamp, A. Kribben, N. F. Roeser, T. Ostrowski, and J. M. Weinberg Alleviation of fatty acid and hypoxia-reoxygenation-induced proximal tubule deenergization by ADP/ATP carrier inhibition and glutamate Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1606 - F1616. [Abstract] [Full Text] [PDF]

				T. Feldkamp, A. Kribben, N. F. Roeser, R. A. Senter, and J. M. Weinberg Accumulation of nonesterified fatty acids causes the sustained energetic deficit in kidney proximal tubules after hypoxia-reoxygenation Am J Physiol Renal Physiol, February 1, 2006; 290(2): F465 - F477. [Abstract] [Full Text] [PDF]

				M. de Graauw, I. Tijdens, R. Cramer, S. Corless, J. F. Timms, and B. van de Water Heat Shock Protein 27 Is the Major Differentially Phosphorylated Protein Involved in Renal Epithelial Cellular Stress Response and Controls Focal Adhesion Organization and Apoptosis J. Biol. Chem., August 19, 2005; 280(33): 29885 - 29898. [Abstract] [Full Text] [PDF]

				T. Feldkamp, A. Kribben, and J. M. Weinberg F1FO-ATPase Activity and ATP Dependence of Mitochondrial Energization in Proximal Tubules after Hypoxia/Reoxygenation J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1742 - 1751. [Abstract] [Full Text] [PDF]

				T. Feldkamp, A. Kribben, and J. M. Weinberg Assessment of mitochondrial membrane potential in proximal tubules after hypoxia-reoxygenation Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1092 - F1102. [Abstract] [Full Text] [PDF]

				T. Feldkamp, A. Kribben, N. F. Roeser, R. A. Senter, S. Kemner, M. A. Venkatachalam, I. Nissim, and J. M. Weinberg Preservation of complex I function during hypoxia-reoxygenation-induced mitochondrial injury in proximal tubules Am J Physiol Renal Physiol, April 1, 2004; 286(4): F749 - F759. [Abstract] [Full Text] [PDF]

				G. K. Kumar and J. B. Klein Analysis of expression and posttranslational modification of proteins during hypoxia J Appl Physiol, March 1, 2004; 96(3): 1178 - 1186. [Abstract] [Full Text] [PDF]

				J. V. Bonventre and J. M. Weinberg Recent Advances in the Pathophysiology of Ischemic Acute Renal Failure J. Am. Soc. Nephrol., August 1, 2003; 14(8): 2199 - 2210. [Full Text] [PDF]

				D. Sinha, Z. Wang, V. R. Price, J. H. Schwartz, and W. Lieberthal Chemical anoxia of tubular cells induces activation of c-Src and its translocation to the zonula adherens Am J Physiol Renal Physiol, March 1, 2003; 284(3): F488 - F497. [Abstract] [Full Text] [PDF]