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

J. Biol. Chem., Vol. 280, Issue 8, 6634-6641, February 25, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/8/6634    most recent M412393200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, J.-S. Articles by Seo, J.-S. Search for Related Content PubMed PubMed Citation Articles by Lee, J.-S. Articles by Seo, J.-S. Social Bookmarking                      What's this?

HSP70 Deficiency Results in Activation of c-Jun N-terminal Kinase, Extracellular Signal-regulated Kinase, and Caspase-3 in Hyperosmolarity-induced Apoptosis^*

Jae-Seon Lee¶, Je-Jung Lee¶, and Jeong-Sun Seo||

From the ILCHUN Molecular Medicine Institute, Medical Research Center and Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine and BK21 Human Life Science, Seoul National University, Seoul 110-799, Korea

In this study we examined the function of heat shock protein 70 (HSP70) in the hyperosmolarity-induced apoptotic pathway using hsp70.1–/–mouse embryonic fibroblasts (MEFs). When the cells were exposed to hyperosmotic stress, an absence of HSP70 negatively affected cell viability. Caspase-9 and caspase-3 were rapidly activated, and extensive cleavage occurred in focal adhesion and cytoskeletal molecules in the hsp70.1–/–MEFs. In contrast, hsp70.1+/+ MEFs exhibited no caspase-9 or caspase-3 activation and finally recovered intact cell morphology when cells were shifted back to an isosmotic state. Because HSP70 might be involved in the regulation of mitogen-activated protein kinase (MAPK) activities with regard to various cellular activities, we also monitored MAPK phosphorylation. The absence of HSP70 affected c-Jun N-terminal kinase phosphorylation. However, it had no effect on p38. Sustained phosphorylation of extracellular signal-regulated kinase (ERK) was observed during the hyperosmolarity-induced apoptosis of hsp70.1–/–MEFs. Inhibition of ERK activity by the treatment of PD98059 accelerated the apoptotic pathway. ERK phosphorylation was precisely correlated with shift of mitogen-activated protein kinase phosphatase-3 from the soluble to insoluble fraction. Our results demonstrate that the inhibitory effect of HSP70 on caspase-3 activation is sufficient to inhibit apoptosis and that HSP70 exhibits regulatory functions to c-Jun N-terminal kinase and ERK phosphorylation in hyperosmolarity-induced apoptosis.

Received for publication, November 2, 2004 , and in revised form, December 6, 2004.

^* 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.

^¶ Contributed equally to this work.

^|| To whom correspondence should be addressed. Tel.: 82-2-740-8246; Fax: 82-2-741-5423; E-mail: jeongsun{at}snu.ac.kr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Matsumoto, P. C. Dimayuga, C. Wang, J. Kirzner, M. Cercek, J. Yano, K.-Y. Chyu, P. K. Shah, and B. Cercek Exogenous heat shock protein-70 inhibits cigarette smoke-induced intimal thickening Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1320 - R1327. [Abstract] [Full Text] [PDF]

				R. Farjo, W. M. Peterson, and M. I. Naash Expression Profiling after Retinal Detachment and Reattachment: A Possible Role for Aquaporin-0 Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 511 - 521. [Abstract] [Full Text] [PDF]

				M. B. Burg, J. D. Ferraris, and N. I. Dmitrieva Cellular Response to Hyperosmotic Stresses Physiol Rev, October 1, 2007; 87(4): 1441 - 1474. [Abstract] [Full Text] [PDF]

				A. I Arroba, A. M Lechuga-Sancho, L. M Frago, J. Argente, and J. A Chowen Cell-specific expression of X-linked inhibitor of apoptosis in the anterior pituitary of streptozotocin-induced diabetic rats J. Endocrinol., January 1, 2007; 192(1): 215 - 227. [Abstract] [Full Text] [PDF]

				E. Schmitt, M. Gehrmann, M. Brunet, G. Multhoff, and C. Garrido Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy J. Leukoc. Biol., January 1, 2007; 81(1): 15 - 27. [Abstract] [Full Text] [PDF]