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Pavlok, 1975; Oikawa and Yanagimachi, 1975)

Resveratrol (5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol), a redox active phytoalexin with a large number of beneficial activities is also known for antibacterial property. However the mechanism of action of resveratrol against bacteria remains unknown. Due to its extensive redox property it was envisaged if reactive oxygen species (ROS) generation by resveratrol could be a reason behind its antibacterial activity. Employing Escherichia coli as a model organism we have evaluated the role of diffusible reactive oxygen species in the events leading to inhibition of this organism by resveratrol. Evidence for the role of ROS in E. coli treated with resveratrol was investigated by direct quantification of ROS by flow cytometry, supplementation with ROS scavengers, depletion of intracellular glutathione, employing mutants devoid of enzymatic antioxidant defences, induction of adaptive response prior to resveratrol challenge and monitoring oxidative stress response elements oxyR, soxS and soxR upon resveratrol treatment. Resveratrol treatment did not result in scavengable ROS generation in E. coli cells. However, evidence towards membrane damage was obtained by potassium leakage (atomic absorption spectrometry) and propidium iodide uptake (flow cytometry and microscopy) as an early event. Based on the comprehensive evidences this study concludes for the first time the antibacterial property of resveratrol against E. coli does not progress via the diffusible ROS but is mediated by site-specific oxidative damage to the cell membrane as the primary event.

The antioxidant activity of an arabinogalactan polysaccharide (TSP) isolated from Tinospora cordifolia, an Indian medicinal plant, was studied. The polysaccharide showed good protection against iron-mediated lipid peroxidation of rat brain homogenate as revealed by the thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxide (LOOH) assays. TSP also provided significant protection to protein against gamma-ray induced damage. The protective action can possibly be explained by its very high reactivity towards DPPH, superoxide radicals and the most damaging of radicals, the hydroxyl radical.

The radioprotective activity of Piper betel ethanolic extract (PE) has been studied using rat liver mitochondria and pBR 322 plasmid DNA as two model in vitro systems. The extract effectively prevented gamma-ray induced lipid peroxidation as assessed by measuring thiobarbituric acid reactive substrates, lipid hydroperoxide and conjugated diene. Likewise, it prevented radiation-induced DNA strand breaks in a concentration dependent manner. The radioprotective activity of PE could be attributed to its hydroxyl and superoxide radicals scavenging property along with its lymphoproliferative activity. The radical scavenging capacity of PE was primarily due to its constituent phenolics, which were isolated and identified as chevibetol and allyl pyrocatechol.

We investigated the physiological role of endogenous MAPKactivating death domain-containing protein (MADD), a splice variant of the IG20 gene, that can interact with TNFR1 in tumor necrosis factor-␣ (TNF␣)-induced activation of NF-B, MAPK, ERK1/2, JNK, and p38. Using exon-specific short hairpin RNAs expressing lentiviruses, we knocked down the expression of all IG20 splice variants or MADD, which is overexpressed in cancer cells. Abrogation of MADD expression rendered cells highly susceptible to TNF␣-induced apoptosis in the absence of cycloheximide. It also resulted in a dramatic loss in TNF␣-induced activation of MAPK without any apparent effect on NF-B activation. This observation was substantiated by an accompanying loss in the activation of p90RSK, a key downstream target of MAPK, whereas the NF-B-regulated interleukin 6 levels remained unaffected. Endogenous MADD knockdown, however, did not affect epidermal growth factor-induced MAPK activation thereby demonstrating the specific requirement of MADD for TNF receptor-mediated MAPK activation. Re-expression of short hairpin RNA-resistant MADD in the absence of endogenous IG20 expression rescued the cells from TNF␣-induced apoptosis. The requirement for MADD was highly specific for TNF␣-induced activation of MAPK but not the related JNK and p38 kinases. Loss of MADD expression resulted in reduced Grb2 and Sos1/2 recruitment to the TNFR1 complex and decreased Ras and MEKK1/2 activation. These results demonstrate the essential role of MADD in protecting cancer cells from TNF␣-induced apoptosis by specifically activating MAPKs through Grb2 and Sos1/2 recruitment, and its potential as a novel cancer therapeutic target.Genes in higher organisms generate alternate transcripts that are translated into closely related proteins with different functions. Perturbations in the tightly regulated alternate splicing of key genes in cancers can result in the accumulation of select splice variants of a particular gene or suppression of others. For instance, some cancers are known to preferentially express the more oncogenic and constitutively active RON⌬ (where RON is recepteur d'origine nantais receptor tyrosine kinase) splice variant of RON receptor tyrosine kinase (1). The study of genes that undergo alternative splicing is therefore likely to unravel novel therapeutic targets against cancer (2-4). The IG20 (insulinoma-glucagonoma) is one such gene previously identified in our laboratory (4) that is implicated in cancer cell survival, proliferation, apoptosis, and other regulated functions through alternative splicing (5-20). The IG20 gene encodes at least six different splice variants (SVs) 3 of which the expression of KIAA0358 and IG20-SV4 isoforms is restricted to certain neuronal tissues (17), with KIAA acting as a Rab3a-GEP (20 -22). The other four, namely IG20pa, MADD, IG20-SV2, and DENN-SV, are expressed more ubiquitously (4). Of these, MADD and DENN-SV are constitutively expressed, whereas the IG20pa and IG20-SV2 may or may not be expressed.Among the IG20 isoforms, ...

The extraction behaviour of nitric acid, uranium(VI), and plutonium (IV) has been investigated using N,N-dihexyloctanamide (DHOA) in n-dodecane. Results indicate that, similar to TBP, the amide extracts HNO" U(VI), and Pu(IV) as HNO,.DHOA, U02(NO,),.2DHOA and Pu(NO,),.2DHOA, respectively, from moderately acidic solutions (35 M HNO,). On the other hand at higher acidities (8.5 M HNO,), similar to tertiary amines, anionic species, U02(NO,),-and PU(NO,),Z-are extracted as [U0 2(NO,r,] [HDHOA+] and [Pu(NO,)l-] [HDHOA+]z, respectively, by ion-pair formation. The basicity of the amide (K H = 0.188), indicated by the equilibrium constant for the uptake of nitric acid is marginally larger than that of TBP (0.160). The third phase formation in H 20-HNO,-0.5 M DHOA-n-dodecane system occurs when nitric acid concentration in the aqueous phase approaches a value of 9 M. The equilibrium constant values (log Kcx) for the formation of U0 2