L-galactono-1, 4-lactone dehydrogenase(GLDH) is an important enzyme that catalyzes the last step of the ascorbate biosynthetic pathways in plants. A full-length c DNA clone encoding GLDH was isolated from potato(Solan...L-galactono-1, 4-lactone dehydrogenase(GLDH) is an important enzyme that catalyzes the last step of the ascorbate biosynthetic pathways in plants. A full-length c DNA clone encoding GLDH was isolated from potato(Solanum tuberosum L. ‘Favorita') leaf and subcloned into a binary vector, p BI121, to construct sense and antisense recombinant plant expression vectors. The recombinants were introduced into potato via Agrobacterium-mediated transformation, and plants were confirmed as transgenic using PCR and quantitative real-time PCR. Two anti-sense potato lines(G1 and G2) and three sense lines(G3, G4 and G5) were obtained. The GLDH activity of G4 and G5 were increased in vivo. Moreover, the ascorbic acid(As A) and dehydroascorbate(DHA) contents were up-regulated in both leaves and tubers. However, the shoots of G1 were suppressed and its leaves were deformed. Additionally, the As A contents in G1 leaves and tubers decreased by 28.8% and 10.3%, respectively. The GLDH activity in leaves treated with L-galactono-1,4- lactone(L-Gal L) increased in all lines, as did the As A and DHA contents. These results indicate that GLDH activity plays an important role in regulating the As A level as well as the growth and development of potato plants.展开更多
Drastic surges in intracellular reactive oxygen species(ROS)induce cell apoptosis,while most chemotherapy drugs lead to the accumulation of ROS.Here,we constructed an organic compound,arsenical N-(4-(1,3,2-dithiarsina...Drastic surges in intracellular reactive oxygen species(ROS)induce cell apoptosis,while most chemotherapy drugs lead to the accumulation of ROS.Here,we constructed an organic compound,arsenical N-(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide(AAZ2),which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer(GC).Mechanistically,by targeting pyruvate dehydrogenase kinase 1(PDK1),AAZ2 caused metabolism alteration and the imbalance of redox homeostasis,followed by the inhibition of phosphoinositide-3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway and leading to the activation of B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)/caspase-9(Cas9)/Cas3 cascades.Importantly,our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft.Overall,our data suggested that AAZ2 could contribute to metabolic abnormalities,leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.展开更多
基金support provided by the National Natural Science Foundation of China(30771473)the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-ASTIP-IVFCAAS)Special Fund for Agroscientific Research in the Public Interest and the Key Laboratory of Horticultural Crop Biology and Germplasm Innovation,Ministry of Agriculture,China
文摘L-galactono-1, 4-lactone dehydrogenase(GLDH) is an important enzyme that catalyzes the last step of the ascorbate biosynthetic pathways in plants. A full-length c DNA clone encoding GLDH was isolated from potato(Solanum tuberosum L. ‘Favorita') leaf and subcloned into a binary vector, p BI121, to construct sense and antisense recombinant plant expression vectors. The recombinants were introduced into potato via Agrobacterium-mediated transformation, and plants were confirmed as transgenic using PCR and quantitative real-time PCR. Two anti-sense potato lines(G1 and G2) and three sense lines(G3, G4 and G5) were obtained. The GLDH activity of G4 and G5 were increased in vivo. Moreover, the ascorbic acid(As A) and dehydroascorbate(DHA) contents were up-regulated in both leaves and tubers. However, the shoots of G1 were suppressed and its leaves were deformed. Additionally, the As A contents in G1 leaves and tubers decreased by 28.8% and 10.3%, respectively. The GLDH activity in leaves treated with L-galactono-1,4- lactone(L-Gal L) increased in all lines, as did the As A and DHA contents. These results indicate that GLDH activity plays an important role in regulating the As A level as well as the growth and development of potato plants.
基金supported by the Wuhan University Zhongnan Hospital Translational Medicine and Interdisciplinary Research Joint Fund(No.ZNJC201910),China.
文摘Drastic surges in intracellular reactive oxygen species(ROS)induce cell apoptosis,while most chemotherapy drugs lead to the accumulation of ROS.Here,we constructed an organic compound,arsenical N-(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide(AAZ2),which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer(GC).Mechanistically,by targeting pyruvate dehydrogenase kinase 1(PDK1),AAZ2 caused metabolism alteration and the imbalance of redox homeostasis,followed by the inhibition of phosphoinositide-3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway and leading to the activation of B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)/caspase-9(Cas9)/Cas3 cascades.Importantly,our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft.Overall,our data suggested that AAZ2 could contribute to metabolic abnormalities,leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.
