Characterisation of expression patterns and functional role of Cactin in early zebrafish development

The immune system of teleost zebrafish (Danio rerio) shows high similarity to mammalian counterparts sharing many innate immune components including Toll-Like Receptors (TLRs), cytokines, chemokines and complement molecules. As in mammals, zebrafish also contains the transcription factor NF-jB that plays dualist roles in innate immunity and early development. Indeed NF-jB members are expressed in different temporal patterns during the early stages of zebrafish embryogenesis indicating that each molecule is involved in specific developmental events. In the present study we employ zebrafish as a model to characterise the expression pattern and role of a novel NF-jB regulator, termed Cactin, in early development. Cactin was first characterised in Drosophila as a new member of the Rel pathway that could affect the generation of dorsal–ventral polarity. To explore the potential developmental role of Cactin in zebrafish, we initially investigated its expression pattern and functional role during early embryonic developmental stages. We detect Cactin expression at all stages of early development and knockdown of Cactin by specific morpholino antisense oligonucleotides causes developmental abnormalities manifested by an overall dysmorphic cellular organisation. These results indicate that Cactin has been highly conserved during evolution and plays a key role in early embryonic development

Characterisation of expression patterns and functional role of Cactin in early zebrafish development

The immune system of teleost zebrafish (Danio rerio) shows high similarity to mammalian counterparts sharing many innate immune components including Toll-Like Receptors (TLRs), cytokines, chemokines and complement molecules. As in mammals, zebrafish also contains the transcription factor NF-jB that plays dualist roles in innate immunity and early development. Indeed NF-jB members are expressed in different temporal patterns during the early stages of zebrafish embryogenesis indicating that each molecule is involved in specific developmental events. In the present study we employ zebrafish as a model to characterise the expression pattern and role of a novel NF-jB regulator, termed Cactin, in early development. Cactin was first characterised in Drosophila as a new member of the Rel pathway that could affect the generation of dorsal–ventral polarity. To explore the potential developmental role of Cactin in zebrafish, we initially investigated its expression pattern and functional role during early embryonic developmental stages. We detect Cactin expression at all stages of early development and knockdown of Cactin by specific morpholino antisense oligonucleotides causes developmental abnormalities manifested by an overall dysmorphic cellular organisation. These results indicate that Cactin has been highly conserved during evolution and plays a key role in early embryonic development

Characterisation of expression patterns and functional role of Cactin in early zebrafish development

The immune system of teleost zebrafish (Danio rerio) shows high similarity to mammalian counterparts sharing many innate immune components including Toll-Like Receptors (TLRs), cytokines, chemokines and complement molecules. As in mammals, zebrafish also contains the transcription factor NF-jB that plays dualist roles in innate immunity and early development. Indeed NF-jB members are expressed in different temporal patterns during the early stages of zebrafish embryogenesis indicating that each molecule is involved in specific developmental events. In the present study we employ zebrafish as a model to characterise the expression pattern and role of a novel NF-jB regulator, termed Cactin, in early development. Cactin was first characterised in Drosophila as a new member of the Rel pathway that could affect the generation of dorsal–ventral polarity. To explore the potential developmental role of Cactin in zebrafish, we initially investigated its expression pattern and functional role during early embryonic developmental stages. We detect Cactin expression at all stages of early development and knockdown of Cactin by specific morpholino antisense oligonucleotides causes developmental abnormalities manifested by an overall dysmorphic cellular organisation. These results indicate that Cactin has been highly conserved during evolution and plays a key role in early embryonic development

Characterisation of expression patterns and functional role of Cactin in early zebrafish development

The immune system of teleost zebrafish (Danio rerio) shows high similarity to mammalian counterparts sharing many innate immune components including Toll-Like Receptors (TLRs), cytokines, chemokines and complement molecules. As in mammals, zebrafish also contains the transcription factor NF-jB that plays dualist roles in innate immunity and early development. Indeed NF-jB members are expressed in different temporal patterns during the early stages of zebrafish embryogenesis indicating that each molecule is involved in specific developmental events. In the present study we employ zebrafish as a model to characterise the expression pattern and role of a novel NF-jB regulator, termed Cactin, in early development. Cactin was first characterised in Drosophila as a new member of the Rel pathway that could affect the generation of dorsal–ventral polarity. To explore the potential developmental role of Cactin in zebrafish, we initially investigated its expression pattern and functional role during early embryonic developmental stages. We detect Cactin expression at all stages of early development and knockdown of Cactin by specific morpholino antisense oligonucleotides causes developmental abnormalities manifested by an overall dysmorphic cellular organisation. These results indicate that Cactin has been highly conserved during evolution and plays a key role in early embryonic development

Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), is a selective anticancer cytokine capable of exerting a targeted therapy approach. Disappointingly, recent research has highlighted the development of TRAIL resistance in cancer cells, thus minimising its usefulness in clinical settings. However, several recent studies have demonstrated that cancer cells can be sensitised to TRAIL through the employment of a combinatorial approach, utilizing TRAIL in conjunction with other natural or synthetic anticancer agents. In the present study, the chemo-sensitising effect of curcumin on TRAIL-induced apoptosis in renal carcinoma cells (RCC) was investigated. The results indicate that exposure of kidney cancer ACHN cells to curcumin sensitised the cells to TRAIL, with the combination treatment of TRAIL and curcumin synergistically targeting the cancer cells without affecting the normal renal proximal tubular epithelial cells (RPTEC/TERT1) cells. Furthermore, this combination treatment was shown to induce caspase-dependent apoptosis, inhibition of the proteasome, induction of ROS, upregulation of death receptor 4 (DR4), alterations in mitogen-activated protein kinase (MAPK) signalling and induction of endoplasmic reticulum stress. An in vivo zebrafish embryo study demonstrated the effectiveness of the combinatorial regime to inhibit tumour formation without affecting zebrafish embryo viability or development. Overall, the results arising from this study demonstrate that curcumin has the ability to sensitise TRAIL-resistant ACHN cells to TRAIL-induced apoptosis

Genetic determinants of hyaloid and retinal vasculature in zebrafish

<p>Abstract</p> <p>Background</p> <p>The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals. Developmental abnormalities or microvascular complications in the retinal vasculature result in severe human eye diseases that lead to blindness. To exploit the advantages of zebrafish for genetic, developmental and pharmacological studies of retinal vasculature, we characterised the intraocular vasculature in zebrafish.</p> <p>Results</p> <p>We show a detailed morphological and developmental analysis of the retinal blood supply in zebrafish. Similar to the transient hyaloid vasculature in mammalian embryos, vessels are first found attached to the zebrafish lens at 2.5 days post fertilisation. These vessels progressively lose contact with the lens and by 30 days post fertilisation adhere to the inner limiting membrane of the juvenile retina. Ultrastructure analysis shows these vessels to exhibit distinctive hallmarks of mammalian retinal vasculature. For example, smooth muscle actin-expressing pericytes are ensheathed by the basal lamina of the blood vessel, and vesicle vacuolar organelles (VVO), subcellular mediators of vessel-retinal nourishment, are present. Finally, we identify 9 genes with cell membrane, extracellular matrix and unknown identity that are necessary for zebrafish hyaloid and retinal vasculature development.</p> <p>Conclusion</p> <p>Zebrafish have a retinal blood supply with a characteristic developmental and adult morphology. Abnormalities of these intraocular vessels are easily observed, enabling application of genetic and chemical approaches in zebrafish to identify molecular regulators of hyaloid and retinal vasculature in development and disease.</p

Summary of differentially expressed genes between 5 versus 3 dpf eyes using GO biological process annotation.

<p>A, B: GO summary for up-regulated genes between 5 versus 3 dpf. C, D: GO summary for down-regulated genes between 5 versus 3 dpf. A, C: pie chart presenting the number of differentially expressed genes in each GO category. B, D: bar plot presenting the significance of each GO term in Q-values. Q-value<0.05 was set as the significance threshold as depicted by the red dashed line.</p