Apoptosis supercedes necrosis in mitochondrial DNA-depleted Jurkat cells by cleavage of receptor-interacting protein and inhibition of lysosomal cathepsin.
In the present study, we used mitochondrial DNA-depleted Jurkat subclones (rho0 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 rho0 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 rho0 cells (ATP-rho0), 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- rho0 cells were blocked by caspase-3 inhibitors. Activities of cathepsins B and D in the lysate of necrotic rho0 cells were inhibited by the addition of apoptotic parental Jurkat cell lysate. Thus, apoptosis may supercede necrosis.
Department of Internal Medicine (Section 4), Sapporo Medical University, School of Medicine, Sapporo, Japan.
Tsutomu
T
Sato
Takuro
T
Machida
Sho
S
Takahashi
Kazuyuki
K
Murase
Yutaka
Y
Kawano
Tsuyoshi
T
Hayashi
Satoshi
S
Iyama
Kohich
K
Takada
Kageaki
K
Kuribayashi
Yasushi
Y
Sato
Masayoshi
M
Kobune
Rishu
R
Takimoto
Takuya
T
Matsunaga
Junji
J
Kato
Yoshiro
Y
Niitsu
D000255:Adenosine Triphosphate / Q000378:metabolism; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002402:Cathepsin D / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D050356:Lipid Metabolism; D008247:Lysosomes / Q000201:enzymology*; D009336:Necrosis; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; C481004:CH-11 anti-fas antibody, human; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D019014:fas Receptor; D000255:Adenosine Triphosphate; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D053148:Caspase 3; D053453:Caspase 9; D002401:Cathepsin B; D002402:Cathepsin D