AIM:To explore the influence of ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate(TPOL)on cell apoptosis and its potential mechanism.METHODS:HEK293T cells sensitive to TPOL were treated with different concentrations of T...AIM:To explore the influence of ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate(TPOL)on cell apoptosis and its potential mechanism.METHODS:HEK293T cells sensitive to TPOL were treated with different concentrations of TPOL with or without exposure to light radiation,before treatment with various inhibitors,N-acetyl-Lcysteine(NAC),pifithrin-αand Z-DVED-FMK.Cell viability was measured by CCK-8 assay.Annexin V/propidium iodide staining was used to count the number of apoptotic cells.DCFH-DA staining was used to detect reactive oxygen species(ROS)levels,and JC-1 staining was used to assess mitochondrial membrane potential by flow cytometry.The expression of apoptosis-related proteins and cell cycle-regulated molecules was measured by Western blot.RESULTS:TPOL enhanced the apoptosis of HEK293T cells in a dose-dependent manner(P<0.05),with a decrease in Bcl-2 and increases in Bax and cytochrome C(Cyto C),followed by up-regulation of activated caspase-9 and caspase-3,and the cleavage of PARP(P<0.05).The TPOL-enhanced cleavage of caspase-3 and PARP was rescued by Z-DVED-FMK(P<0.01).TPOL also led to a rapid increase in ROS,a reduction in mitochondrial membrane potential,and the release of Cyto C(P<0.01),all of which could be reversed by the ROS scavenger NAC.Moreover,the TPOL-caused alterations in p21,p27,Rb,and CDK2 were also recovered by the p53 inhibitor pifithrin-α(P<0.05).The TPOL-induced changes in Bax,Bcl-2,cleaved caspase-9,activated caspase-3,and cleaved PARP were subsequently rescued by pretreatment with pifithrin-α(P<0.05).CONCLUSION:TPOL can induce cellular apoptosis with ROS-mediated mitochondrial membrane damage through the activation of a ROS-dependent p53/p21/p27/Rb/Bax/Cyto C/caspase-mediated signal axis.展开更多
Two title compounds, 4,4?diformyl-diphenoxyethane (compound 1, C16H14O4) and 4,4?4创-triformyl-triphenoxytriethylamine (compound 2, C27H27NO6), were synthesized by condensation of 4-hydroxybenzaldehyde with 1,2-dichlo...Two title compounds, 4,4?diformyl-diphenoxyethane (compound 1, C16H14O4) and 4,4?4创-triformyl-triphenoxytriethylamine (compound 2, C27H27NO6), were synthesized by condensation of 4-hydroxybenzaldehyde with 1,2-dichloroethane and tris(2-chloroethyl)amine, respectively in dimethyl formamide in the presence of anhydrous potassium carbonate. The crystal data are: monoclinic, P21/c, a = 7.571(2), b = 12.608(3), c = 7.357(2) ? b = 105.823(6)? V = 675.7(2) 3, Mr = 270.3, Z = 2, Dc = 1.328 g/cm3, F(000) = 284, m(MoKa) = 0.096 mm-1, R = 0.0537 and wR = 0.2189 for compound 1; and monoclinic, P21/n, a = 11.7162(6), b = 9.0042(6), c = 22.908(2) ? b = 99.505(1)? V = 2383.5(3) ?, Mr = 461.50, Z = 4, Dc = 1.286 g/cm3, F(000)= 976, m(MoKa) = 0.091 mm-1, R = 0.0464 and wR = 0.1462 for compound 2. The molecule of compound 1 (dialdehyde) is located at the crystallographic inversion center nearby the midpoint of C(8)C(8A) single bond. The three chains in the molecule of compound 2 (trialdehyde) are of non-crystallographic pseudo-C3 symmetry, and each of them is quite planar.展开更多
基金Supported by the National Natural Science Foundation of China(No.81172824)。
文摘AIM:To explore the influence of ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate(TPOL)on cell apoptosis and its potential mechanism.METHODS:HEK293T cells sensitive to TPOL were treated with different concentrations of TPOL with or without exposure to light radiation,before treatment with various inhibitors,N-acetyl-Lcysteine(NAC),pifithrin-αand Z-DVED-FMK.Cell viability was measured by CCK-8 assay.Annexin V/propidium iodide staining was used to count the number of apoptotic cells.DCFH-DA staining was used to detect reactive oxygen species(ROS)levels,and JC-1 staining was used to assess mitochondrial membrane potential by flow cytometry.The expression of apoptosis-related proteins and cell cycle-regulated molecules was measured by Western blot.RESULTS:TPOL enhanced the apoptosis of HEK293T cells in a dose-dependent manner(P<0.05),with a decrease in Bcl-2 and increases in Bax and cytochrome C(Cyto C),followed by up-regulation of activated caspase-9 and caspase-3,and the cleavage of PARP(P<0.05).The TPOL-enhanced cleavage of caspase-3 and PARP was rescued by Z-DVED-FMK(P<0.01).TPOL also led to a rapid increase in ROS,a reduction in mitochondrial membrane potential,and the release of Cyto C(P<0.01),all of which could be reversed by the ROS scavenger NAC.Moreover,the TPOL-caused alterations in p21,p27,Rb,and CDK2 were also recovered by the p53 inhibitor pifithrin-α(P<0.05).The TPOL-induced changes in Bax,Bcl-2,cleaved caspase-9,activated caspase-3,and cleaved PARP were subsequently rescued by pretreatment with pifithrin-α(P<0.05).CONCLUSION:TPOL can induce cellular apoptosis with ROS-mediated mitochondrial membrane damage through the activation of a ROS-dependent p53/p21/p27/Rb/Bax/Cyto C/caspase-mediated signal axis.
基金The authors thank the financial support of the Natural Science Foundation of Fujian Province (No. E0110010)
文摘Two title compounds, 4,4?diformyl-diphenoxyethane (compound 1, C16H14O4) and 4,4?4创-triformyl-triphenoxytriethylamine (compound 2, C27H27NO6), were synthesized by condensation of 4-hydroxybenzaldehyde with 1,2-dichloroethane and tris(2-chloroethyl)amine, respectively in dimethyl formamide in the presence of anhydrous potassium carbonate. The crystal data are: monoclinic, P21/c, a = 7.571(2), b = 12.608(3), c = 7.357(2) ? b = 105.823(6)? V = 675.7(2) 3, Mr = 270.3, Z = 2, Dc = 1.328 g/cm3, F(000) = 284, m(MoKa) = 0.096 mm-1, R = 0.0537 and wR = 0.2189 for compound 1; and monoclinic, P21/n, a = 11.7162(6), b = 9.0042(6), c = 22.908(2) ? b = 99.505(1)? V = 2383.5(3) ?, Mr = 461.50, Z = 4, Dc = 1.286 g/cm3, F(000)= 976, m(MoKa) = 0.091 mm-1, R = 0.0464 and wR = 0.1462 for compound 2. The molecule of compound 1 (dialdehyde) is located at the crystallographic inversion center nearby the midpoint of C(8)C(8A) single bond. The three chains in the molecule of compound 2 (trialdehyde) are of non-crystallographic pseudo-C3 symmetry, and each of them is quite planar.
