| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* School of Biological Sciences and
Department of Medicine, University of Liverpool, Liverpool, United Kingdom
Mcl-1 is an antiapoptotic member of the Bcl-2 family of proteins that plays a central role in cell survival of neutrophils and other cells. The protein is unusual among family members in that it has a very short half-life of 2–3 h. In this report, we show that sodium salicylate (at 10 mM) greatly enhances the rate at which neutrophils undergo apoptosis and, in parallel, greatly accelerates the turnover rate of Mcl-1, decreasing its half-life to only 90 min. Whereas constitutive and GM-CSF-modified Mcl-1 turnover is regulated by the proteasome, the accelerated sodium salicylate-induced Mcl-1 turnover is mediated largely via caspases. Sodium salicylate resulted in rapid activation of caspase-3, -8, -9, and -10, and salicylate-accelerated Mcl-1 turnover was partly blocked by caspase inhibitors. Sodium salicylate also induced dramatic changes in the activities of members of the MAPK family implicated in Mcl-1 turnover and apoptosis. For example, sodium salicylate blocked GM-CSF-stimulated Erk and Akt activation, but resulted in rapid and sustained activation of p38-MAPK, an event mimicked by okadaic acid that also accelerates Mcl-1 turnover and neutrophil apoptosis. These data thus shed important new insights into the dynamic and highly regulated control of neutrophil apoptosis that is effected by modification in the rate of Mcl-1 turnover.
This article has been cited by other articles:
|
|
 |
|
  A. Paunel-Gorgulu, M. Zornig, T. Logters, J. Altrichter, U. Rabenhorst, J. Cinatl, J. Windolf, and M. Scholz Mcl-1-Mediated Impairment of the Intrinsic Apoptosis Pathway in Circulating Neutrophils from Critically Ill Patients Can Be Overcome by Fas Stimulation J. Immunol., November 15, 2009; 183(10): 6198 - 6206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Dyugovskaya, A. Polyakov, P. Lavie, and L. Lavie Delayed Neutrophil Apoptosis in Patients with Sleep Apnea Am. J. Respir. Crit. Care Med., March 1, 2008; 177(5): 544 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cross, R. J. Moots, and S. W. Edwards The dual effects of TNF{alpha} on neutrophil apoptosis are mediated via differential effects on expression of Mcl-1 and Bfl-1 Blood, January 15, 2008; 111(2): 878 - 884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Yang, V. Kaushal, S. V. Shah, and G. P. Kaushal Mcl-1 is downregulated in cisplatin-induced apoptosis, and proteasome inhibitors restore Mcl-1 and promote survival in renal tubular epithelial cells Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1710 - F1717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Dzhagalov, A. St. John, and Y.-W. He The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages Blood, February 15, 2007; 109(4): 1620 - 1626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Negrotto, E. Malaver, M. E. Alvarez, N. Pacienza, L. P. D'Atri, R. G. Pozner, R. M. Gomez, and M. Schattner Aspirin and Salicylate Suppress Polymorphonuclear Apoptosis Delay Mediated by Proinflammatory Stimuli J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 972 - 979. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
