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

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services 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 Sato, T. Articles by Niitsu, Y. Search for Related Content PubMed PubMed Citation Articles by Sato, T. Articles by Niitsu, Y.

Apoptosis Supercedes Necrosis in Mitochondrial DNA-Depleted Jurkat Cells by Cleavage of Receptor-Interacting Protein and Inhibition of Lysosomal Cathepsin¹

Department of Internal Medicine (Section 4), Sapporo Medical University, School of Medicine, Sapporo, Japan

In the present study, we used mitochondrial DNA-depleted Jurkat subclones (⁰ cells) to demonstrate that Fas agonistic Ab (CH-11), at the concentrations that evoke apoptotic death of the parental Jurkat cells, induced necrosis mainly through generation of excess reactive oxygen species, lysosomal rupture, and sequential activation of cathepsins B and D, and in minor part through activation of receptor-interacting protein (RIP). In the ⁰ cells treated with CH-11, ATP supplementation converted necrosis into apoptosis by the formation of the apoptosome and subsequent activation of procaspase-3. In these ATP-supplemented ⁰ cells (ATP-⁰), generation of excess ROS and lysosomal rupture were still seen, yet cathepsins B and D were inactivated and RIP was degraded. The conversion of necrosis to apoptosis, RIP degradation, and cathepsin inactivation in ATP- ⁰ cells were blocked by caspase-3 inhibitors. Activities of cathepsins B and D in the lysate of necrotic ⁰ cells were inhibited by the addition of apoptotic parental Jurkat cell lysate. Thus, apoptosis may supercede necrosis.

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.

¹ This study was supported in part by the Japan Society for the Promotion of Science.

² Address correspondence and reprint requests to Dr. Yoshiro Niitsu, Department of Internal Medicine (Section 4), Sapporo Medical University, School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan. E-mail address: niitsu{at}sapmed.ac.jp

³ Abbreviations used in this paper: ROS, reactive oxygen species; AO, acridine orange; COX, cytochrome oxidase subunit; E-64d, epoxysuccinyl-L-leucylamido-3-methyl-butane ethyl ester; HE, hydroethidine; MnSOD, manganese superoxide dismutase; MPT, mitochondrial permeability transition; mtDNA, mitochondrial DNA; NAC, N-acetyl-L-cysteine; PI, propidium iodide; pNA, p-nitroanilide; RIP, receptor-interacting protein; RIPKO, RIP knocked down; siRNA, short interfering RNA; SOD, superoxide dismutase; Z-DEVD-FMK, N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethyl ketone.

This article has been cited by other articles:

				R. S. Hotchkiss, A. Strasser, J. E. McDunn, and P. E. Swanson Cell Death N. Engl. J. Med., October 15, 2009; 361(16): 1570 - 1583. [Full Text] [PDF]

				S. E. Lutz, Y. Zhao, M. Gulinello, S. C. Lee, C. S. Raine, and C. F. Brosnan Deletion of Astrocyte Connexins 43 and 30 Leads to a Dysmyelinating Phenotype and Hippocampal CA1 Vacuolation J. Neurosci., June 17, 2009; 29(24): 7743 - 7752. [Abstract] [Full Text] [PDF]