Objective Isoliquiritigenin （ISL）, a licorice chalconoid, is considered to be a bioactive agent with chemopreventive potential. This study investigates the mechanisms involved in ISL-induced apoptosis in human cervi...Objective Isoliquiritigenin （ISL）, a licorice chalconoid, is considered to be a bioactive agent with chemopreventive potential. This study investigates the mechanisms involved in ISL-induced apoptosis in human cervical carcinoma HeLa cells. Methods Cell viability was evaluated using a 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyl-tetrazolium bromide （MTT） assay. Apoptosis was determined by flow cytometry using an Annexin V-FITC Apoptosis Detection Kit. The intracetlular ROS levels were assessed using a 2, 7-dichlorofluorescein probe assay. The mitochondrial membrane potential was measured with the dual-emission potential-sensitive probe 5, 5＇, 6, 6＇-tetra-chloro-1, 1＇, 3, 3＇-tetraethyl-imidacarbocyanine iodide （JC-1）. The degradation of poly-ADP-ribose polymerase （PARP） protein, the phosphorylation of PKR-like ER kinase （PERK）, the phosphorylation of the a-subunit of eukaryotic initiation factor 2 （elF2a）, the expression of the 78 kD glucose-regulated protein （GRP 78）, and the activation of caspase-12 were analyzed via western blot analysis. Results ISL significantly inhibited the proliferation, the increase in ROS levels and apoptotic rates of HeLa cells in a concentration-dependent manner. Moreover, ISL induced mitochondrial dysfunction, caspase activation, and PARP cleavage, which displayed features of mitochondria dependent on apoptotic signals. Besides, exposure of HeLa cells to ISL triggered endoplasmic reticulum （ER） stress, as indicated by the increase in p-elF2a and GRP78 expression, ER stress-dependent apoptosis is caused by the activation of ER-specific caspase-12. Conclusion The findings from our study suggest that ISL-induced oxidative stress causes HeLa cel apoptosis via the mitochondrion-dependent and the ER stress-triggered signaling pathways.展开更多
Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed pr...Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group （P〈0.01）, while obviously reduced the MDA and PCO contents and the RO$ levels derived from of the brain mitochondria.展开更多
The dynamic assembly of microtubules plays a key role in maintaining structural and functional integrity of eukaryotic cel s,especial y with regard to neuronal differentiation or neurite outgrowth and synaptic plastic...The dynamic assembly of microtubules plays a key role in maintaining structural and functional integrity of eukaryotic cel s,especial y with regard to neuronal differentiation or neurite outgrowth and synaptic plasticity,which contribute to the development of the nervous system and memory formation.展开更多
基金supported by the National Natural Science Foundation of China (No. 30960451)Major State Basic Research Development Program (2010CB535003)the Xinjiang production and construction corps funds for distinguished young scientists to ZHENG Qiu Sheng,international cooperation projects (2012BC001)
文摘Objective Isoliquiritigenin （ISL）, a licorice chalconoid, is considered to be a bioactive agent with chemopreventive potential. This study investigates the mechanisms involved in ISL-induced apoptosis in human cervical carcinoma HeLa cells. Methods Cell viability was evaluated using a 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyl-tetrazolium bromide （MTT） assay. Apoptosis was determined by flow cytometry using an Annexin V-FITC Apoptosis Detection Kit. The intracetlular ROS levels were assessed using a 2, 7-dichlorofluorescein probe assay. The mitochondrial membrane potential was measured with the dual-emission potential-sensitive probe 5, 5＇, 6, 6＇-tetra-chloro-1, 1＇, 3, 3＇-tetraethyl-imidacarbocyanine iodide （JC-1）. The degradation of poly-ADP-ribose polymerase （PARP） protein, the phosphorylation of PKR-like ER kinase （PERK）, the phosphorylation of the a-subunit of eukaryotic initiation factor 2 （elF2a）, the expression of the 78 kD glucose-regulated protein （GRP 78）, and the activation of caspase-12 were analyzed via western blot analysis. Results ISL significantly inhibited the proliferation, the increase in ROS levels and apoptotic rates of HeLa cells in a concentration-dependent manner. Moreover, ISL induced mitochondrial dysfunction, caspase activation, and PARP cleavage, which displayed features of mitochondria dependent on apoptotic signals. Besides, exposure of HeLa cells to ISL triggered endoplasmic reticulum （ER） stress, as indicated by the increase in p-elF2a and GRP78 expression, ER stress-dependent apoptosis is caused by the activation of ER-specific caspase-12. Conclusion The findings from our study suggest that ISL-induced oxidative stress causes HeLa cel apoptosis via the mitochondrion-dependent and the ER stress-triggered signaling pathways.
基金supported by Key Program of National Natural Science Foundation of China(U1432248)National Natural Science Foundation of China(11175222,11305226)
文摘Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group （P〈0.01）, while obviously reduced the MDA and PCO contents and the RO$ levels derived from of the brain mitochondria.
基金supported by the National Science Foundation of China[31870333]the Taishan Scholar Program of Shandong Province[tshw201502046]+3 种基金Shandong Provincial Science Foundation[ZR2019MH094]Yantai ShuangBai Scholar ProgramQinghai Province Applied Basic Research Project[2020-ZJ-905]the Open Project of State Key Laboratory of Plateau Ecology and Agriculture,Qinghai University[2018-KF-05]。
文摘The dynamic assembly of microtubules plays a key role in maintaining structural and functional integrity of eukaryotic cel s,especial y with regard to neuronal differentiation or neurite outgrowth and synaptic plasticity,which contribute to the development of the nervous system and memory formation.
