| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Renal Section, Department of Medicine, Boston University Medical Center, Boston, Massachusetts 02118; and 2 Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, Michigan 48202
We have examined the role of reactive oxygen species (ROS) in apoptosis induced by growth factor deprivation in primary cultures of mouse proximal tubular (MPT) cells. When confluent monolayers of MPT cells are deprived of all growth factors, the cells die by apoptosis over a 10- and 14-day period. Both epidermal growth factor (EGF) and high-dose insulin directly inhibit apoptosis of MPT cells deprived of growth factors. Growth factor deprivation results in an increase in the cellular levels of superoxide anion while apoptosis of MPT cells induced by growth factor withdrawal is inhibited by a number of antioxidants and scavengers of ROS. Growth factor deprivation also results in activation of caspase activity, which is inhibited by EGF and high-dose insulin as well as by the ROS scavengers and antioxidants that inhibit apoptosis. The cell-permeant caspase inhibitor, z-Val-Ala-Asp-CH2F (zVAD-fmk), prevents the increase in caspase activity and markedly inhibits apoptosis induced by growth factor deprivation. However, zVAD-fmk had no effect on the increased levels of superoxide associated with growth factor deprivation. Thus we provide novel evidence that ROS play an important role in mediating apoptosis associated with growth factor deprivation. ROS appear to act upstream of caspases in the apoptotic pathway. We hypothesize that oxidant stress, induced by growth factor withdrawal, represents a signaling mechanism for the default pathway of apoptosis.
cell viability; survival factors; programmed cell death; reactive oxygen species; caspases
This article has been cited by other articles:
|
|
 |
|
  D. Sinha, Z. Wang, K. L. Ruchalski, J. S. Levine, S. Krishnan, W. Lieberthal, J. H. Schwartz, and S. C. Borkan Lithium activates the Wnt and phosphatidylinositol 3-kinase Akt signaling pathways to promote cell survival in the absence of soluble survival factors Am J Physiol Renal Physiol, April 1, 2005; 288(4): F703 - F713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Kaushal, L. Liu, V. Kaushal, X. Hong, O. Melnyk, R. Seth, R. Safirstein, and S. V. Shah Regulation of caspase-3 and -9 activation in oxidant stress to RTE by forkhead transcription factors, Bcl-2 proteins, and MAP kinases Am J Physiol Renal Physiol, December 1, 2004; 287(6): F1258 - F1268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pareja, O. Sanchez, J. Lorita, M. Soley, and I. Ramirez Activated epidermal growth factor receptor (ErbB1) protects the heart against stress-induced injury in mice Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R455 - R462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Berlanga, P. Prats, D. Remirez, R. Gonzalez, P. Lopez-Saura, J. Aguiar, M. Ojeda, J. J. Boyle, A. J. Fitzgerald, and R. J. Playford Prophylactic Use of Epidermal Growth Factor Reduces Ischemia/Reperfusion Intestinal Damage Am. J. Pathol., August 1, 2002; 161(2): 373 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-B. Kwon, J.-Y. Yang, D.-G. Ryu, H.-W. Rho, J.-S. Kim, J.-W. Park, H.-R. Kim, and B.-H. Park Vibrio vulnificus Cytolysin Induces Superoxide Anion-initiated Apoptotic Signaling Pathway in Human ECV304 Cells J. Biol. Chem., December 7, 2001; 276(50): 47518 - 47523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Davis, H. S. Nick, and A. Agarwal Manganese Superoxide Dismutase Attenuates Cisplatin-Induced Renal Injury: Importance of Superoxide J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2683 - 2690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Touyz and E. L. Schiffrin Signal Transduction Mechanisms Mediating the Physiological and Pathophysiological Actions of Angiotensin II in Vascular Smooth Muscle Cells Pharmacol. Rev., December 1, 2000; 52(4): 639 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Iglesias, V. E. Abernethy, Z. Wang, W. Lieberthal, J. S. Koh, and J. S. Levine Albumin is a major serum survival factor for renal tubular cells and macrophages through scavenging of ROS Am J Physiol Renal Physiol, November 1, 1999; 277(5): F711 - F722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Bertrand, C. Desbois-Mouthon, A. Cadoret, C. Prunier, H. Robin, J. Capeau, A. Atfi, and G. Cherqui Insulin Antiapoptotic Signaling Involves Insulin Activation of the Nuclear Factor kappa B-dependent Survival Genes Encoding Tumor Necrosis Factor Receptor-associated Factor 2 and Manganese-superoxide Dismutase J. Biol. Chem., October 22, 1999; 274(43): 30596 - 30602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Matute-Bello, W. C. Liles, K. P. Steinberg, P. A. Kiener, S. Mongovin, E. Y. Chi, M. Jonas, and T. R. Martin Soluble Fas Ligand Induces Epithelial Cell Apoptosis in Humans with Acute Lung Injury (ARDS) J. Immunol., August 15, 1999; 163(4): 2217 - 2225. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
