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.
Sato
Tsutomu
T
Department of Internal Medicine (Section 4), Sapporo Medical University, School of Medicine, Sapporo, Japan.
Machida
Takuro
T
Takahashi
Sho
S
Murase
Kazuyuki
K
Kawano
Yutaka
Y
Hayashi
Tsuyoshi
T
Iyama
Satoshi
S
Takada
Kohich
K
Kuribayashi
Kageaki
K
Sato
Yasushi
Y
Kobune
Masayoshi
M
Takimoto
Rishu
R
Matsunaga
Takuya
T
Kato
Junji
J
Niitsu
Yoshiro
Y
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