| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Renal Section, Department of Medicine, Boston Medical Center, Boston, MA, USA
2 Department of Nephrology, First Affiliated Hospital, Zhongshan University, GuangZhou, China
3 Section of Gastroenterology, Boston Medical Center, Boston, MA, USA
4 Department of Pathology, Tufts University and New England Medical Center, Boston, MA, USA
5 Department of Molecular Biology and Genetics, University of Guelph, Toronto, Ontario, Canada
* To whom correspondence should be addressed. E-mail: sborkan{at}bu.edu.
Inhibition of the mitochondrial release and nuclear translocation of apoptosis inducing factor (AIF) by hsp72 may ameliorate apoptosis in renal epithelial cells exposed to a metabolic inhibitor. To evaluate this hypothesis, cells were transiently exposed to 5mM NaCN in the absence of medium glucose, a maneuver known to induce apoptosis. ATP depletion for 1-2 hr. resulted in the progressive accumulation of mitochondrial AIF in the cytosol of samples obtained by selectively permeabilizing the plasma membrane with digitonin. During recovery from ATP depletion, time-dependent nuclear AIF accumulation (but not cytochrome c, an F0F1 ATP synthase subunit or talin) was observed in isolated nuclei. Nuclear AIF accumulation was associated with peripheral chromatin condensation and DNA degradation. Prior heat stress (HS) significantly reduced AIF leakage into the cytosol, decreased nuclear accumulation of AIF and inhibited DNA degradation. HS also increased the interaction between AIF and hsp72 detected by immunoprecipitation. In ATP depleted cells, selective over-expression of human hsp72 reduced the leakage of mitochondrial AIF in a dose-dependent manner (r = 0.997). This study suggests that mitochondrial membrane injury and subsequent AIF release contribute to nuclear injury and apoptosis in ATP depleted renal cells. Hsp72, an anti-apoptotic protein, inhibits cell injury in part, by preventing mitochondrial AIF release and perhaps by decreasing its nuclear accumulation.
This article has been cited by other articles:
|
|
 |
|
  Z. Wang, A. Havasi, J. M. Gall, H. Mao, J. H. Schwartz, and S. C. Borkan {beta}-Catenin Promotes Survival of Renal Epithelial Cells by Inhibiting Bax J. Am. Soc. Nephrol., September 1, 2009; 20(9): 1919 - 1928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Mao, Z. Li, Y. Zhou, Z. Li, S. Zhuang, X. An, B. Zhang, W. Chen, J. Nie, Z. Wang, et al. HSP72 attenuates renal tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy Am J Physiol Renal Physiol, July 1, 2008; 295(1): F202 - F214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Havasi, Z. Li, Z. Wang, J. L. Martin, V. Botla, K. Ruchalski, J. H. Schwartz, and S. C. Borkan Hsp27 Inhibits Bax Activation and Apoptosis via a Phosphatidylinositol 3-Kinase-dependent Mechanism J. Biol. Chem., May 2, 2008; 283(18): 12305 - 12313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chassin, M. Bens, J. de Barry, R. Courjaret, J. L. Bossu, F. Cluzeaud, S. Ben Mkaddem, M. Gibert, B. Poulain, M. R. Popoff, et al. Pore-forming epsilon toxin causes membrane permeabilization and rapid ATP depletion-mediated cell death in renal collecting duct cells Am J Physiol Renal Physiol, September 1, 2007; 293(3): F927 - F937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Brooks, J. Wang, T. Yang, and Z. Dong Characterization of cell clones isolated from hypoxia-selected renal proximal tubular cells Am J Physiol Renal Physiol, January 1, 2007; 292(1): F243 - F252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Christensen, Y.-H. Kim, T.-H. Kwon, and S. Nielsen Lithium treatment induces a marked proliferation of primarily principal cells in rat kidney inner medullary collecting duct Am J Physiol Renal Physiol, July 1, 2006; 291(1): F39 - F48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Devarajan Update on Mechanisms of Ischemic Acute Kidney Injury J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1503 - 1520. [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Johnson and M. Fleshner Releasing signals, secretory pathways, and immune function of endogenous extracellular heat shock protein 72 J. Leukoc. Biol., March 1, 2006; 79(3): 425 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Dokladny, P. L. Moseley, and T. Y. Ma Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G204 - G212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Riordan, R. Sreedharan, S. Wang, G. Thulin, A. Mann, M. Stankewich, S. Van Why, M. Kashgarian, and N. J. Siegel HSP70 binding modulates detachment of Na-K-ATPase following energy deprivation in renal epithelial cells Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1236 - F1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Peng, X. Guo, S. C. Borkan, A. Bharti, Y. Kuramochi, S. Calderwood, and D. B. Sawyer Heat Shock Protein 90 Stabilization of ErbB2 Expression Is Disrupted by ATP Depletion in Myocytes J. Biol. Chem., April 1, 2005; 280(13): 13148 - 13152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wei, J. Wang, M.-H. Wang, F. Yu, and Z. Dong Inhibition of apoptosis by Zn2+ in renal tubular cells following ATP depletion Am J Physiol Renal Physiol, September 1, 2004; 287(3): F492 - F500. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
