Programmed cell death （apoptosis） is a key host response to virus infection. Viruses that can modulate host apoptotic responses are likely to gain important opportunities for transmission. Here we review recent stud...Programmed cell death （apoptosis） is a key host response to virus infection. Viruses that can modulate host apoptotic responses are likely to gain important opportunities for transmission. Here we review recent studies that demonstrate that particles of Invertebrate iridescent virus 6 （IIV-6） （Iridoviridae, genus Iridovirus）, or an IIV-6 virion protein extract, are capable of inducing apoptosis in lepidopteran and coleopteran cells, at concentrations 1000-fold lower than that required to shut-off host macromolecular synthesis. Induction of apoptosis depends on endocytosis of one or more heat-sensitive virion component（s）. Studies with a JNK inhibitor （SP600125） indicated that the JNK signaling pathway is significantly involved in apoptosis in IIV-6 infections of Choristoneurafumiferana cells. The genome of IIV-6 codes for an inhibitor of apoptosis iap gene （193R） that encodes a protein of 208 aa with 15% identity and 28% similarity in its amino acid sequence to IAP-3 from Cydia pomonella ganulovirus （CpGV）. Transcription of IIV-6 iap did not require prior DNA or protein synthesis, indicating that it is an immediate-early class gene. Transient expression and gene knockdown studies have confirmed the functional nature of the IIV-6 lap gene. We present a tentative model for IIV-6 induction and inhibition of apoptosis in insect cells and discuss the potential applications of these findings in insect pest control.展开更多
LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transa...LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transactivates LEF1/TCF-mediated transcriptions during dorsalization. Although LEF-mediated transcription is also implicated in ventralization, the underlying molecular mechanism is not well understood. Using the vertebrate Xenopus laevis model system, we found that Xom, which is a ventralizing homeobox protein with dual roles of transcriptional activation and repression, forms a complex with LEF 1/TCF through its homeodomain and transactivates LEF 1/TCF-mediated transcription through its N-terminal transactivation domain （TAD）. Our data show that Xom lacking the N-terminal TAD fails to transactivate ventral genes, such as BMP4 and Xom itself, but retains the ability to suppress transcriptional activation of dorsal gene promoters, such as the Goosecoid promoter, indicating that transactivation and repression are separable functions of Xom. It has been postulated that Xom forms a positive re-enforcement loop with BMP4 to promote ventral- ization and to suppress dorsal gene expression. Consistent with an essential role of Xom transactivation of LEF1/TCFs during early embryogenesis, we found that expression of the dominant-negative Xom mutant that lacks the TAD fails to re-enforce the ventral signaling of BMP4 and causes a catastrophic effect during gastrulation. Our data suggest that the functional interaction of Xom and LEF 1/TCF-factors is essential for ventral cell fate determination and that LEF 1/TCF factors may function as a point of convergence to mediate the combined signaling of Wnt/β-catenin and BMP4/Xom pathways during early embryogenesis.展开更多
Objective: To investigate Caspase-3 expression and its role in neuronal apoptosis.Methods: The T13-L2 spinal cord of rats was injured by traction after the amplitude of P1-N1 wave, monitored by a cortical somatosensor...Objective: To investigate Caspase-3 expression and its role in neuronal apoptosis.Methods: The T13-L2 spinal cord of rats was injured by traction after the amplitude of P1-N1 wave, monitored by a cortical somatosensory evoked potential (CSEP) monitor, decreased to seventy percent of that before operation. Then rats were killed in 6 h, 1 d, 4 d, 7 d, 14 d and 21 d respectively after operation. Flow cytometer terminal deoxynucleotldyl transferease-mediated biotinylated deoxynuridine triphosphate nick end labeling (TUNEL), Caspase-3 activity assay and immunohistochemical method were applied to investigate Caspase-3 expression in the spinal cord tissue and to study neuronal apoptosis in rats. Results: After spinal cord injury, apoptotic cells detected by flow cytometry and TUNEL-positive cells were significantly more, and positive immunohistochemical staining of Caspase-3 and Caspase-3 activity were significantly higher in Group injury than in Groups control and laminectomy, respectively (P> 0.05, P> 0.01). Similar trend of changes was noticed in apoptotic cells, TUNEL-positive cells and positive immunohistochemical staining of Caspase-3, all of which reached their respective peak 7 days after operation. Caspase-3 activity reached its peak, however, 4 days postoperatively. Conclusions: Increased expression and activity of Caspase-3 protein in neurons after tractive spinal cord injury is the biochemical signal of early spinal cell apoptosis. It is of great significance for understanding the mechanism of spinal cord injury.展开更多
Vertebrate development culminates in the generation of proper proportions of a large variety of different cell types and subtypes essential for tissue,organ and system functions in the right place at the right time.Fo...Vertebrate development culminates in the generation of proper proportions of a large variety of different cell types and subtypes essential for tissue,organ and system functions in the right place at the right time.Foxn4,a member of the forkhead box/winged-helix transcription factor superfamily,is expressed in mitotic progenitors and/or postmitotic precursors in both neural(e.g.,retina and spinal cord)and non-neural tissues(e.g.,atrioventricular canal and proximal airway).During development of the central nervous system,Foxn4 is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating Dll4-Notch signaling.Moreover,it activates Dll4-Notch signaling to drive commitment of p2 progenitors to the V2b and V2c interneuron fates during spinal cord neurogenesis.In development of non-neural tissues,Foxn4 plays an essential role in the specification of the atrioventricular canal and is indirectly required for patterning the distal airway during lung development.In this review,we highlight current understanding of the structure,expression and developmental functions of Foxn4 with an emphasis on its cell-autonomous and non-cell-autonomous roles in different tissues and animal model systems.展开更多
基金SLB was supported in part by Research Enhancement FundsResearch Development Funds from the Office of the Vice-President for Research, Texas Tech University and the Texas Higher Education Coordin-ating Boardprovided by the Depar-tment of Biological Sciences at Texas Tech University
文摘Programmed cell death （apoptosis） is a key host response to virus infection. Viruses that can modulate host apoptotic responses are likely to gain important opportunities for transmission. Here we review recent studies that demonstrate that particles of Invertebrate iridescent virus 6 （IIV-6） （Iridoviridae, genus Iridovirus）, or an IIV-6 virion protein extract, are capable of inducing apoptosis in lepidopteran and coleopteran cells, at concentrations 1000-fold lower than that required to shut-off host macromolecular synthesis. Induction of apoptosis depends on endocytosis of one or more heat-sensitive virion component（s）. Studies with a JNK inhibitor （SP600125） indicated that the JNK signaling pathway is significantly involved in apoptosis in IIV-6 infections of Choristoneurafumiferana cells. The genome of IIV-6 codes for an inhibitor of apoptosis iap gene （193R） that encodes a protein of 208 aa with 15% identity and 28% similarity in its amino acid sequence to IAP-3 from Cydia pomonella ganulovirus （CpGV）. Transcription of IIV-6 iap did not require prior DNA or protein synthesis, indicating that it is an immediate-early class gene. Transient expression and gene knockdown studies have confirmed the functional nature of the IIV-6 lap gene. We present a tentative model for IIV-6 induction and inhibition of apoptosis in insect cells and discuss the potential applications of these findings in insect pest control.
文摘LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transactivates LEF1/TCF-mediated transcriptions during dorsalization. Although LEF-mediated transcription is also implicated in ventralization, the underlying molecular mechanism is not well understood. Using the vertebrate Xenopus laevis model system, we found that Xom, which is a ventralizing homeobox protein with dual roles of transcriptional activation and repression, forms a complex with LEF 1/TCF through its homeodomain and transactivates LEF 1/TCF-mediated transcription through its N-terminal transactivation domain （TAD）. Our data show that Xom lacking the N-terminal TAD fails to transactivate ventral genes, such as BMP4 and Xom itself, but retains the ability to suppress transcriptional activation of dorsal gene promoters, such as the Goosecoid promoter, indicating that transactivation and repression are separable functions of Xom. It has been postulated that Xom forms a positive re-enforcement loop with BMP4 to promote ventral- ization and to suppress dorsal gene expression. Consistent with an essential role of Xom transactivation of LEF1/TCFs during early embryogenesis, we found that expression of the dominant-negative Xom mutant that lacks the TAD fails to re-enforce the ventral signaling of BMP4 and causes a catastrophic effect during gastrulation. Our data suggest that the functional interaction of Xom and LEF 1/TCF-factors is essential for ventral cell fate determination and that LEF 1/TCF factors may function as a point of convergence to mediate the combined signaling of Wnt/β-catenin and BMP4/Xom pathways during early embryogenesis.
文摘Objective: To investigate Caspase-3 expression and its role in neuronal apoptosis.Methods: The T13-L2 spinal cord of rats was injured by traction after the amplitude of P1-N1 wave, monitored by a cortical somatosensory evoked potential (CSEP) monitor, decreased to seventy percent of that before operation. Then rats were killed in 6 h, 1 d, 4 d, 7 d, 14 d and 21 d respectively after operation. Flow cytometer terminal deoxynucleotldyl transferease-mediated biotinylated deoxynuridine triphosphate nick end labeling (TUNEL), Caspase-3 activity assay and immunohistochemical method were applied to investigate Caspase-3 expression in the spinal cord tissue and to study neuronal apoptosis in rats. Results: After spinal cord injury, apoptotic cells detected by flow cytometry and TUNEL-positive cells were significantly more, and positive immunohistochemical staining of Caspase-3 and Caspase-3 activity were significantly higher in Group injury than in Groups control and laminectomy, respectively (P> 0.05, P> 0.01). Similar trend of changes was noticed in apoptotic cells, TUNEL-positive cells and positive immunohistochemical staining of Caspase-3, all of which reached their respective peak 7 days after operation. Caspase-3 activity reached its peak, however, 4 days postoperatively. Conclusions: Increased expression and activity of Caspase-3 protein in neurons after tractive spinal cord injury is the biochemical signal of early spinal cell apoptosis. It is of great significance for understanding the mechanism of spinal cord injury.
基金supported in part by Sun Yat-sen University,Zhongshan Ophthalmic Center,and the National Institutes of Health(EY020849 and EY012020 to XiangMengQing)
文摘Vertebrate development culminates in the generation of proper proportions of a large variety of different cell types and subtypes essential for tissue,organ and system functions in the right place at the right time.Foxn4,a member of the forkhead box/winged-helix transcription factor superfamily,is expressed in mitotic progenitors and/or postmitotic precursors in both neural(e.g.,retina and spinal cord)and non-neural tissues(e.g.,atrioventricular canal and proximal airway).During development of the central nervous system,Foxn4 is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating Dll4-Notch signaling.Moreover,it activates Dll4-Notch signaling to drive commitment of p2 progenitors to the V2b and V2c interneuron fates during spinal cord neurogenesis.In development of non-neural tissues,Foxn4 plays an essential role in the specification of the atrioventricular canal and is indirectly required for patterning the distal airway during lung development.In this review,we highlight current understanding of the structure,expression and developmental functions of Foxn4 with an emphasis on its cell-autonomous and non-cell-autonomous roles in different tissues and animal model systems.
