TY - JOUR
T1 - Activation of the caspase cascade during Stx1-induced apoptosis in Burkitt's lymphoma cells
AU - Ahdjoudj, S.
AU - Lasmoles, F.
AU - Oyajobi, B. O.
AU - Lomri, A.
AU - Delannoy, Ph
AU - Marie, P. J.
PY - 2001
Y1 - 2001
N2 - Shiga toxin 1 (Stx1) produced by Escherichia coli has been reported to induce apoptosis in many different cell types, including Burkitt's lymphoma (BL) cells. Since it has been established that the caspases play essential roles as the effector molecules in the apoptotic process in most cases, we examined the kinetics of caspase activation during the process of Stx1-mediated apoptosis of BL cells. Using Ramos BL cells that are highly sensitive to Stx1-mediated cytotoxicity, we observed that multiple caspases, including caspase-3, -7, and -8 were promptly activated following Stx1 treatment, as indicated by both the procaspase cleavages and enhancement of cleavage of the tetrapeptide substrates of the caspases. In addition, the inhibition assay revealed that caspase-8 is located upstream of both caspase-3 and -7, suggesting that Stx1-mediated apoptosis utilizes a similar caspase cascade to that involved in Fas-mediated apoptosis. Neither anti-Fas mAb nor TNF-α, however, affected the Stx1-mediated apoptosis of Ramos cells, Although the precise mechanism of Stx1-mediated activation of caspase-8 is still unclear, we have demonstrated that crosslinkage of CD77, a functional receptor for Stx1, with specific antibody is sufficient to induce activation of caspase-8. Our findings should provide new insight into the understanding of the molecular basis of Stx1-mediated cell injury.
AB - Shiga toxin 1 (Stx1) produced by Escherichia coli has been reported to induce apoptosis in many different cell types, including Burkitt's lymphoma (BL) cells. Since it has been established that the caspases play essential roles as the effector molecules in the apoptotic process in most cases, we examined the kinetics of caspase activation during the process of Stx1-mediated apoptosis of BL cells. Using Ramos BL cells that are highly sensitive to Stx1-mediated cytotoxicity, we observed that multiple caspases, including caspase-3, -7, and -8 were promptly activated following Stx1 treatment, as indicated by both the procaspase cleavages and enhancement of cleavage of the tetrapeptide substrates of the caspases. In addition, the inhibition assay revealed that caspase-8 is located upstream of both caspase-3 and -7, suggesting that Stx1-mediated apoptosis utilizes a similar caspase cascade to that involved in Fas-mediated apoptosis. Neither anti-Fas mAb nor TNF-α, however, affected the Stx1-mediated apoptosis of Ramos cells, Although the precise mechanism of Stx1-mediated activation of caspase-8 is still unclear, we have demonstrated that crosslinkage of CD77, a functional receptor for Stx1, with specific antibody is sufficient to induce activation of caspase-8. Our findings should provide new insight into the understanding of the molecular basis of Stx1-mediated cell injury.
KW - Apoptosis
KW - Burkitt's lymphoma
KW - CD77
KW - Caspase
KW - Shiga toxin
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U2 - 10.1002/1097-4644(20010401)81:1<128::AID-JCB1029>3.0.CO;2-G
DO - 10.1002/1097-4644(20010401)81:1<128::AID-JCB1029>3.0.CO;2-G
M3 - Article
C2 - 11180403
AN - SCOPUS:0035097223
SN - 0730-2312
VL - 81
SP - 128
EP - 142
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
IS - 1
ER -