|
Originally published In Press as doi:10.1074/jbc.M412708200 on June 8, 2005
J. Biol. Chem., Vol. 280, Issue 33, 29885-29898, August 19, 2005
Heat Shock Protein 27 Is the Major Differentially Phosphorylated Protein Involved in Renal Epithelial Cellular Stress Response and Controls Focal Adhesion Organization and Apoptosis*
Marjo de Graauw ,
Ine Tijdens,
Rainer Cramer ,
Steve Corless¶,
John F. Timms¶||, and
Bob van de Water**
From the
Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, 2300 RA Leiden, The Netherlands, The BioCentre, University of Reading, Whiteknights, P. O. Box 221, Reading, Berkshire RG6 6AS United Kingdom, ¶Ludwig Institute for Cancer Research and the ||Department of Biochemistry and Molecular Biology, University College London, Gower Street, London, WC1E 6BT, United Kingdom
We used two-dimensional difference gel electrophoresis to determine early changes in the stress-response pathways that precede focal adhesion disorganization linked to the onset of apoptosis of renal epithelial cells. Treatment of LLC-PK1 cells with the model nephrotoxicant 1,2-(dichlorovinyl)-L-cysteine (DCVC) resulted in a >1.5-fold up- and down-regulation of 14 and 9 proteins, respectively, preceding the onset of apoptosis. Proteins included those involved in metabolism, i.e. aconitase and pyruvate dehydrogenase, and those related to stress responses and cytoskeletal reorganization, i.e. cofilin, Hsp27, and  -b-crystallin. The most prominent changes were found for Hsp27, which was related to a pI shift in association with an altered phosphorylation status of serine residue 82. Although both p38 and JNK were activated by DCVC, only inhibition of p38 with SB203580 reduced Hsp27 phosphorylation, which was associated with accelerated reorganization of focal adhesions, cell detachment, and apoptosis. In contrast, inhibition of JNK with SP600125 maintained cell adhesion as well as protection against apoptosis. Active JNK co-localized at focal adhesions after DCVC treatment in a FAK-dependent manner. Inhibition of active JNK localization at focal adhesions did not prevent DCVC-induced phosphorylation of Hsp27. Overexpression of a phosphorylation-defective mutant Hsp27 acted as a dominant negative and accelerated the DCVC-induced changes in the focal adhesions as well as the onset of apoptosis. Our data fit a model whereby early p38 activation results in a rapid phosphorylation of Hsp27, a requirement for proper maintenance of cell adhesion, thus suppressing renal epithelial cell apoptosis.
Received for publication, November 10, 2004
, and in revised form, May 27, 2005.
* This work was supported in part by Netherlands Organization for Scientific Research Grants 902-21-217 and 911-02-22. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
** Supported by a fellowship of the Royal Netherlands Academy for Arts and Sciences. To whom correspondence should be addressed: Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Einsteinweg 55, P. O. Box 9502, 2300 RA Leiden, The Netherlands. Tel.: 31-71-5276223; Fax: 31-71-5274277; E-mail: b.water{at}LACDR.LeidenUniv.nl.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Dai, M. Patel-Chamberlin, R. Natarajan, I. Todorov, J. Ma, J. LaPage, L. Phillips, C. C. Nast, D. Becerra, P. Chuang, et al.
Heat Shock Protein 27 Overexpression Mitigates Cytokine-Induced Islet Apoptosis and Streptozotocin-Induced Diabetes
Endocrinology,
July 1, 2009;
150(7):
3031 - 3039.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. P. Thirone, P. Speight, M. Zulys, O. D. Rotstein, K. Szaszi, S. F. Pedersen, and A. Kapus
Hyperosmotic stress induces Rho/Rho kinase/LIM kinase-mediated cofilin phosphorylation in tubular cells: key role in the osmotically triggered F-actin response
Am J Physiol Cell Physiol,
March 1, 2009;
296(3):
C463 - C475.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Stetler, G. Cao, Y. Gao, F. Zhang, S. Wang, Z. Weng, P. Vosler, L. Zhang, A. Signore, S. H. Graham, et al.
Hsp27 Protects against Ischemic Brain Injury via Attenuation of a Novel Stress-Response Cascade Upstream of Mitochondrial Cell Death Signaling
J. Neurosci.,
December 3, 2008;
28(49):
13038 - 13055.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Vidyasagar, S. Reese, Z. Acun, D. Hullett, and A. Djamali
HSP27 is involved in the pathogenesis of kidney tubulointerstitial fibrosis
Am J Physiol Renal Physiol,
September 1, 2008;
295(3):
F707 - F716.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Merrick
The plasma proteome, adductome and idiosyncratic toxicity in toxicoproteomics research
Brief Funct Genomic Proteomic,
February 12, 2008;
(2008)
eln004v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. de Graauw, I. Tijdens, M. B. Smeets, P. J. Hensbergen, A. M. Deelder, and B. van de Water
Annexin A2 Phosphorylation Mediates Cell Scattering and Branching Morphogenesis via Cofilin Activation
Mol. Cell. Biol.,
February 1, 2008;
28(3):
1029 - 1040.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Zhang, M. Lun, C. M. Schworer, T. M. Blasick, K. K. Masker, J. B. Jones, and D. J. Carey
Heat Shock Protein Expression Is Highly Sensitive to Ischemia-Reperfusion Injury in Rat Kidneys
Ann. Clin. Lab. Sci.,
January 1, 2008;
38(1):
57 - 64.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Salinthone, M. Ba, L. Hanson, J. L. Martin, A. J. Halayko, and W. T. Gerthoffer
Overexpression of human Hsp27 inhibits serum-induced proliferation in airway smooth muscle myocytes and confers resistance to hydrogen peroxide cytotoxicity
Am J Physiol Lung Cell Mol Physiol,
November 1, 2007;
293(5):
L1194 - L1207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Y. Ma, G. H. Tesch, R. A. Flavell, R. J. Davis, and D. J. Nikolic-Paterson
MKK3-p38 signaling promotes apoptosis and the early inflammatory response in the obstructed mouse kidney
Am J Physiol Renal Physiol,
November 1, 2007;
293(5):
F1556 - F1563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Korrapati, J. Chilakapati, F. A. Witzmann, C. Rao, E. A. Lock, and H. M. Mehendale
Proteomics of S-(1, 2-dichlorovinyl)-L-cysteine-induced acute renal failure and autoprotection in mice
Am J Physiol Renal Physiol,
October 1, 2007;
293(4):
F994 - F1006.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Huang, J. B. Fileta, T. Filippopoulos, A. Ray, A. Dobberfuhl, and C. L. Grosskreutz
Hsp27 Phosphorylation in Experimental Glaucoma
Invest. Ophthalmol. Vis. Sci.,
September 1, 2007;
48(9):
4129 - 4135.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Wu, H. Kausar, P. Johnson, D. E. Montoya-Durango, M. Merchant, and M. J. Rane
Hsp27 Regulates Akt Activation and Polymorphonuclear Leukocyte Apoptosis by Scaffolding MK2 to Akt Signal Complex
J. Biol. Chem.,
July 27, 2007;
282(30):
21598 - 21608.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. de Graauw, S. Le Devedec, I. Tijdens, M. B. Smeets, A. M. Deelder, and B. van de Water
Proteomic Analysis of Alternative Protein Tyrosine Phosphorylation in 1,2-Dichlorovinyl-Cysteine-Induced Cytotoxicity in Primary Cultured Rat Renal Proximal Tubular Cells
J. Pharmacol. Exp. Ther.,
July 1, 2007;
322(1):
89 - 100.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Jovceva, M. R. Larsen, M. D. Waterfield, B. Baum, and J. F. Timms
Dynamic cofilin phosphorylation in the control of lamellipodial actin homeostasis
J. Cell Sci.,
June 1, 2007;
120(11):
1888 - 1897.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Martin-Ventura, V. Nicolas, X. Houard, L. M. Blanco-Colio, A. Leclercq, J. Egido, R. Vranckx, J.-B. Michel, and O. Meilhac
Biological Significance of Decreased HSP27 in Human Atherosclerosis
Arterioscler. Thromb. Vasc. Biol.,
June 1, 2006;
26(6):
1337 - 1343.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Cao, N. Dronadula, F. Rizvi, Q. Li, K. Srivastava, W. T. Gerthoffer, and G. N. Rao
Novel Role for STAT-5B in the Regulation of Hsp27-FGF-2 Axis Facilitating Thrombin-Induced Vascular Smooth Muscle Cell Growth and Motility
Circ. Res.,
April 14, 2006;
98(7):
913 - 922.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|
