TY - JOUR
T1 - α-Tocopherol-mediated caspase-3 up-regulation enhances susceptibility to apoptotic stimuli
AU - Miyoshi, Noriyuki
AU - Naniwa, Kisa
AU - Kumagai, Takeshi
AU - Uchida, Koji
AU - Osawa, Toshihiko
AU - Nakamura, Yoshimasa
PY - 2005/8/26
Y1 - 2005/8/26
N2 - Although α-tocopherol is known as an essential micronutrient involved in various oxidative stress-related processes, its non-antioxidant activities have only been characterized in recent years. In this study, we reveal that (+)-α-tocopherol [RRR-α-tocopherol] enhances cellular susceptibility to both oxidative and non-oxidative apoptosis-inducing stimuli through up-regulation of caspase-3/CPP32 expression in several human cell lines. Exposure of (+)-α-tocopherol pretreated cells to known apoptosis-inducing stimuli, such as Fas, H2O2, or etoposide, resulted in an increase in cellular apoptotsis. In addition, (+)-α-tocopherol also elevated the pro-caspase-3 protein level and mRNA expression in a time- and dose-dependent manner, while other tocopherol analogues showed no effect. Experiments using a GC-specific DNA binding agent, mithramycin A, and an electrophoretic mobility shift assay demonstrated that Sp1 might mediate the enhanced expression of caspase-3. Our results also confirmed that (+)-α-tocopherol promotes the expression, but not the activation, of caspase-3 in various human cell lines. These findings provide biological evidence showing that (+)-α-tocopherol can amplify the apoptotic response by up-regulating the expression of pro-caspase-3.
AB - Although α-tocopherol is known as an essential micronutrient involved in various oxidative stress-related processes, its non-antioxidant activities have only been characterized in recent years. In this study, we reveal that (+)-α-tocopherol [RRR-α-tocopherol] enhances cellular susceptibility to both oxidative and non-oxidative apoptosis-inducing stimuli through up-regulation of caspase-3/CPP32 expression in several human cell lines. Exposure of (+)-α-tocopherol pretreated cells to known apoptosis-inducing stimuli, such as Fas, H2O2, or etoposide, resulted in an increase in cellular apoptotsis. In addition, (+)-α-tocopherol also elevated the pro-caspase-3 protein level and mRNA expression in a time- and dose-dependent manner, while other tocopherol analogues showed no effect. Experiments using a GC-specific DNA binding agent, mithramycin A, and an electrophoretic mobility shift assay demonstrated that Sp1 might mediate the enhanced expression of caspase-3. Our results also confirmed that (+)-α-tocopherol promotes the expression, but not the activation, of caspase-3 in various human cell lines. These findings provide biological evidence showing that (+)-α-tocopherol can amplify the apoptotic response by up-regulating the expression of pro-caspase-3.
KW - Apoptosis
KW - Caspase-3
KW - Etoposide
KW - Sp 1
KW - α-Tocopherol
UR - http://www.scopus.com/inward/record.url?scp=22144472568&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22144472568&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.06.113
DO - 10.1016/j.bbrc.2005.06.113
M3 - Article
C2 - 16009347
AN - SCOPUS:22144472568
VL - 334
SP - 466
EP - 473
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -