TY - JOUR
T1 - Molecular mechanisms of apoptosis induction by 2-dodecylcyclobutanone, a radiolytic product of palmitic acid, in human lymphoma U937 cells
AU - Yu, Da Yong
AU - Zhao, Qing Li
AU - Furuta, Masakazu
AU - Todoriki, Setsuko
AU - Izumi, Keisuke
AU - Yamakage, Kohji
AU - Matsumoto, Kozo
AU - Nomura, Takaharu
AU - Kondo, Takashi
N1 - Funding Information:
Acknowledgment This work was supported in part by grants provided by Food Safety Commission, the Cabinet Office, Japan.
PY - 2012/6
Y1 - 2012/6
N2 - The irradiation of fat-containing food forms 2-dodecylcyclobutanone (2-DCB) from palmitic acid (PA). In this study, we investigated whether 2-DCB and PA induce apoptosis in human lymphoma U937 cells. We found that cell viability decreased by 2-DCB and apoptosis was induced by 2-DCB and PA. 2-DCB and PA significantly enhanced the formation of intracellular reactive oxygen species (ROS). Apoptosis induced by 2-DCB and PA was strongly prevented by an antioxidant, N-acetyl-l-cysteine. The treatment with 2-DCB and PA resulted in the loss of mitochondrial membrane potential, and Fas, caspase-8 and caspase-3 activation. Pretreatment with a pan-caspase inhibitor (z-VAD) significantly inhibited apoptosis induced by 2-DCB and PA. Moreover, 2-DCB and PA also induced Bax up-regulation, the reduction in Bcl-2 expression level, Bid cleavage and the release of cytochrome c from the mitochondria to the cytosol. In addition, an increase in intracellular Ca 2+ concentration ([Ca 2+] i) was observed after the treatment with 2-DCB and PA. Our results indicated that intracellular ROS generation, the modulation of the Fas-mitochondrion-caspase-dependent pathway and the increase in [Ca 2+] i involved in apoptosis are induced by 2-DCB and PA in U937 cells.
AB - The irradiation of fat-containing food forms 2-dodecylcyclobutanone (2-DCB) from palmitic acid (PA). In this study, we investigated whether 2-DCB and PA induce apoptosis in human lymphoma U937 cells. We found that cell viability decreased by 2-DCB and apoptosis was induced by 2-DCB and PA. 2-DCB and PA significantly enhanced the formation of intracellular reactive oxygen species (ROS). Apoptosis induced by 2-DCB and PA was strongly prevented by an antioxidant, N-acetyl-l-cysteine. The treatment with 2-DCB and PA resulted in the loss of mitochondrial membrane potential, and Fas, caspase-8 and caspase-3 activation. Pretreatment with a pan-caspase inhibitor (z-VAD) significantly inhibited apoptosis induced by 2-DCB and PA. Moreover, 2-DCB and PA also induced Bax up-regulation, the reduction in Bcl-2 expression level, Bid cleavage and the release of cytochrome c from the mitochondria to the cytosol. In addition, an increase in intracellular Ca 2+ concentration ([Ca 2+] i) was observed after the treatment with 2-DCB and PA. Our results indicated that intracellular ROS generation, the modulation of the Fas-mitochondrion-caspase-dependent pathway and the increase in [Ca 2+] i involved in apoptosis are induced by 2-DCB and PA in U937 cells.
KW - 2-Dodecylcyclobutanone
KW - Apoptosis
KW - Calcium
KW - Palmitic acid
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=84862487293&partnerID=8YFLogxK
U2 - 10.1007/s10495-012-0698-1
DO - 10.1007/s10495-012-0698-1
M3 - 学術論文
C2 - 22311471
AN - SCOPUS:84862487293
SN - 1360-8185
VL - 17
SP - 636
EP - 645
JO - Apoptosis
JF - Apoptosis
IS - 6
ER -