Toxic Effect of Powdered Castor Oil Seed (Ricinus Communis L.) on Roof Rat

The powder of castor oil seed of (Ricinus communis L. Euphorbiaceae) was used in a Laboratory experiment for its toxicity. The study was undertaken to investigate the effect of powdered castor oil seed (Ricinus communis L.) on roof rat. Forty five roof rat were caught and divided into three (3) groups, there were five (5) roof rat in a cage which represent a group, replicated three (3) times were used in the study. The castor oil seed was turned to powdery form using pestle and mortal to grind the seeds. Three feed formulations were used; A baited formulation of powdered castor oil seed plus fried fish at ratio 1:0.5; Another baited powdered castor oil seed plus fried fish at ratio 1:0.1; The third group were given a commercial rat feed only which serve as control. These feeds were administered to each group of the roof rat and their behaviors were properly monitored over a period of five (5) days. The histology of the kidney, liver, spleen, which was initially preserved in formalin were later analysed. The results showed that a powdered castor oil seed baited with fried fish can serve as rodenticide and all test groups show histological features of lethal tissue damage in all the organs examined while control group shows normal tissue. Key words: Toxic effect, Castor oil seed, Roof rat, kidney, liver, spleen, feed

Chemical analysis of Ricinus communis L. (Euphorbiaceace) seed kernel extract and its in-vitro toxicity in two Podagrica Species (Coleoptera: Chrysomelidae)

Since synthetic pesticides are associated with many toxicological problems against untargeted subjects, pesticides from botanical sources become a better option. This study obtained R. communis seed kernel extract (RCSKE) through acidified aqueous extraction. The extract was screened using Infra red (IR) and Ultraviolet (UV) spectroscopy, High-Performance Liquid Chromatography (HPLC) and Cass Chromatography (GC) for bioactive agents. In-vitro effects of RCSKE, chlorpyrifos (CPF) and cypermethrin (CYPER-M) on superoxide dismutase (SOD), Catalase (CAT), acetylcholinesterase (AChE) and Carboxylesterase (CE) activities in Podagrica sjosdteti and Podagrica uniforma were determined spectrophotometrically. The IR and UV of RCSKE majorly depict the presence of aromatic ring, ethylenic bond, carbonyl bond, hydroxyl and carboxylic groups. The HPLC and GC majorly show the presence of ricinoleic acid, ricinine and ricin. The RCSKE, CYPER-M and CPF increased CAT activity in P. sjosdteti, but reduced it in P. uniforma. The RCSKE and CYPER-M significantly reduced SOD, and elevated AChE activities in P. sjosdteti. The IC50 values of RCSKE, CYPER-M and CPF against CE activity in P. sjosdteti were IC50 = 2.66 µg/ml, IC50 = 2.37µg/ml and IC50 = 2.65 µg/ml), respectively, while that of RCSKE against P. uniforma was IC50 = 2.49 µg/ml. This study suggests that the extract of Ricinus communis seed kernel contains bioactive substances, capable to inhibit the antioxidant, acetylcholinesterase and carboxylesterase enzymes in Podagrica species flea beetles, comparable to commercial pesticides, Cypermethrin and Chlorpyrifos. Key words: Ricinus communis, Chemical screening, Podagrica sjosdteti, Podagrica uniforma, antioxidant enzymes, hydrolytic enzymes DOI: 10.7176/ALST/75-05 Publication date:June 30th 2019

Regulation of secretory transport by protein kinase D–mediated phosphorylation of the ceramide transfer protein

Protein kinase D (PKD) has been identified as a crucial regulator of secretory transport at the trans-Golgi network (TGN). Recruitment and activation of PKD at the TGN is mediated by the lipid diacylglycerol, a pool of which is generated by sphingomyelin synthase from ceramide and phosphatidylcholine. The nonvesicular transfer of ceramide from the endoplasmic reticulum to the Golgi complex is mediated by the lipid transfer protein CERT (ceramide transport). In this study, we identify CERT as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT toward its lipid target phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity, identifying PKD as a regulator of lipid homeostasis. We also show that CERT, in turn, is critical for PKD activation and PKD-dependent protein cargo transport to the plasma membrane. Thus, the interdependence of PKD and CERT is key to the maintenance of Golgi membrane integrity and secretory transport

A WXW Motif Is Required for the Anticancer Activity of the TAT-RasGAP317-326 Peptide.

TAT-RasGAP317-326, a cell-permeable 10-amino acid-long peptide derived from the N2 fragment of p120 Ras GTPase-activating protein (RasGAP), sensitizes tumor cells to apoptosis induced by various anticancer therapies. This RasGAP-derived peptide, by targeting the deleted in liver cancer-1 (DLC1) tumor suppressor, also hampers cell migration and invasion by promoting cell adherence and by inhibiting cell movement. Here, we systematically investigated the role of each amino acid within the RasGAP317-326 sequence for the anticancer activities of TAT-RasGAP317-326. We report here that the first three amino acids of this sequence, tryptophan, methionine, and tryptophan (WMW), are necessary and sufficient to sensitize cancer cells to cisplatin-induced apoptosis and to reduce cell migration. The WMW motif was found to be critical for the binding of fragment N2 to DLC1. These results define the interaction mode between the active anticancer sequence of RasGAP and DLC1. This knowledge will facilitate the design of small molecules bearing the tumor-sensitizing and antimetastatic activities of TAT-RasGAP317-326

Caffeine Inhibits EGF-Stimulated Trophoblast Cell Motility through the Inhibition of mTORC2 and Akt.

Impaired trophoblast invasion is associated with pregnancy disorders such as early pregnancy loss and preeclampsia. There is evidence to suggest that the consumption of caffeine during pregnancy may increase the risk of pregnancy loss; however, little is known about the direct effect of caffeine on normal trophoblast biology. Our objectives were to examine the effect of caffeine on trophoblast migration and motility after stimulation with epidermal growth factor (EGF) and to investigate the intracellular signaling pathways involved in this process. Primary first-trimester extravillous trophoblasts (EVT) and the EVT-derived cell line SGHPL-4 were used to study the effect of caffeine on EGF-stimulated cellular motility using time-lapse microscopy. SGHPL-4 cells were further used to study the effect of caffeine and cAMP on EGF-stimulated invasion of fibrin gels. The influence of caffeine and cAMP on EGF-stimulated intracellular signaling pathways leading to the activation of Akt were investigated by Western blot analysis. Caffeine inhibits both EGF-stimulated primary EVT and SGHPL-4 cell motility. EGF stimulation activates phosphatidylinositol 3-kinase, and Akt and caffeine inhibit this activation. Although cAMP inhibits both motility and invasion, it does not inhibit the activation of Akt, indicating that the effects of caffeine seen in this study are independent of cAMP. Further investigation indicated a role for mammalian target of rapamycin complex 2 (mTORC2) as a target for the inhibitory effect of caffeine. In conclusion, we demonstrate that caffeine inhibits EGF-stimulated trophoblast invasion and motility in vitro and so could adversely influence trophoblast biology in vivo

A global microRNA screen identifies regulators of the ErbB receptor signaling network

Background: The growth factor heregulin (HRG) potently stimulates epithelial cell survival and proliferation through the binding of its cognate receptor ErbB3 (also known as HER3). ErbB3-dependent signal transmission relies on the dimerization partner ErbB2, a receptor tyrosine kinase that is frequently overexpressed and/or amplified in breast cancer cells. Substantial evidence suggests that deregulated ErbB3 expression also contributes to the transformed phenotype of breast cancer cells. Results: By genome-wide screening, we identify 43 microRNAs (miRNAs) that specifically impact HRG-induced activation of the PI3K-Akt pathway. Bioinformatic analysis combined with experimental validation reveals a highly connected molecular miRNA-gene interaction network particularly for the negative screen hits. For selected miRNAs, namely miR-149, miR-148b, miR-326, and miR-520a-3p, we demonstrate the simultaneous downregulation of the ErbB3 receptor and multiple downstream signaling molecules, explaining their efficient dampening of HRG responses and ascribing to these miRNAs potential context-dependent tumor suppressive functions. Conclusions: Given the contribution of HRG signaling and the PI3K-Akt pathway in particular to tumorigenesis, this study not only provides mechanistic insight into the function of miRNAs but also has implications for future clinical applications

Vaccinia-induced epidermal growth factor receptor-MEK signalling and the anti-apoptotic protein F1L synergize to suppress cell death during infection

F1L is a functional Bcl-2 homologue that inhibits apoptosis at the mitochondria during vaccinia infection. However, the extent and timing of cell death during ΔF1L virus infection suggest that additional viral effectors cooperate with F1L to limit apoptosis. Here we report that vaccinia growth factor (VGF), a secreted virulence factor, promotes cell survival independently of its role in virus multiplication. Analysis of single and double knockout viruses reveals that VGF acts synergistically with F1L to protect against cell death during infection. Cell survival in the absence of F1L is dependent on VGF activation of the epidermal growth factor receptor. Furthermore, signalling through MEK kinases is necessary and sufficient for VGF-dependent survival. We conclude that VGF stimulates an epidermal growth factor receptor-MEK-dependent pro-survival pathway that synergizes with F1L to counteract an infection-induced apoptotic pathway that predominantly involves the BH3-only protein Bad

Tailoring Chimeric Ligands for Studying and Biasing ErbB Receptor Family Interactions

Described is the development and application of a versatile semisynthetic strategy, based on a combination of sortase-mediated coupling and tetrazine ligation chemistry, which can be exploited for the efficient incorporation of tunable functionality into chimeric recombinant proteins. To demonstrate the scope of the method, the assembly of a set of bivalent ligands, which integrate members of the epidermal growth factor (EGF) ligand family, is described. By using a series of bivalent EGFs with variable intraligand spacing, the differences in structure were correlated with the ability to bias signaling in the ErbB receptor family in a cell motility assay. Biasing away from EGFR-HER2 dimerization with a bivalent EGF was observed to reduce cell motility in an intraligand distance-dependent fashion, thus demonstrating the utility of the approach for acutely perturbing receptor-mediated cell signaling pathways.National Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant U54-CA112967)National Institutes of Health (U.S.) (R01DE019523-13)Massachusetts Institute of Technology. Computational and Systems Biology Program. MIT-Merck Postdoctoral FellowshipSwiss National Science Foundation (Postdoctoral Fellowship)National Institute of Environmental Health Sciences (Training Grant in Environmental Toxicology 5-T32-ES007020