Antiproliferative function of glia maturation factor beta.

Recombinant human glia maturation factor beta (GMF-beta) reversibly inhibits the proliferation of neoplastic cells in culture by arresting the cells in the G0/G1 phase. This phenomenon is not target-cell specific, as neural and nonneural cells are equally inhibited. When tested simultaneously, GMF-beta suppresses the mitogenic effect of acidic fibroblasts growth factor (aFGF), but the two are synergistic in promoting the morphologic differentiation of cultured astrocytes. GMF-beta also counteracts the growth-stimulating effect of pituitary extract and cholera toxin on Schwann cells. The results underscore the regulatory role of GMF-beta and its intricate interaction with the mitogenic growth factors.     

Effect of imipramine hydrochloride on the activity of gamma-aminobutyric acid transaminase in regions of the rat brain

The effect of intraperitoneal injection of imipramine hydrochloride on the activity of gamma-aminobutyric acid transaminase was determined in three regions of the rat brain.The cerebral hemispheres did not show a significant change in the activity of gamma-aminobutyric acid transaminase. Cerebellum and brain stem, both, however, showed a very significant decrease in the activity of the enzyme at 15 and 30 minutes after drug administration. At 90 minutes after drug administration, the activity of gamma-aminobutyric acid transaminase had returned to nearly control values.     

The modifying effect of manganese on the enzymic profiles and pathways of carbohydrate metabolism in rat liver and adipose tissue during development

The effect of Mn²⁺ on the pattern of emergence of enzymes in rat liver and adipose tissue was studied in weaned rats given a milk diet (high fat) or sucrose-casein diet (high carbohydrate) for three weeks. Addition of Mn²⁺ to the high fat diet was associated with induction of key glycolytic, lipogenic and pentose pathway enzymes in both liver and adipose tissue; parallel increases were found in the incorporation of [1-¹⁴C] glucose into lipid and CO₂. Mn²⁺ induced a change in the profile of enzyme activity similar in pattern to that found in rats given a high sucrose diet or that produced by insulin treatment. Mn²⁺ appears partially to overcome the regulatory feed-back mechanisms of the high fat diet and to provide a signal for the coordinated increase of glucose catabolic and lipogenic processes.     

Inactivation of (Na-++K-+)-stimulated ATPase by a cytotoxic protein from cobra venom in relation to its lytic effects on cells.

The mechanism of action of the cytotoxic protein P6 isolated from cobra venom (Naja naja) which shows preferential cytotoxicity particularly to Yoshida sarcoma cells has been studied by its effects on the membrane-bound enzyme (Na-++K-+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) of a variety of cell systems. Evidence obtained with Yoshida sarcoma cells, dog and human erythrocytes and three tissue culture cell lines KB (human oral carcinoma), Hela (human cervix carcinoma) and L-132 (human lung embryonic) shows that inhibition of (Na-++K-+)-ATPase by the P6 protein can be correlated with its lytic activity. (Na-++k-+)-ATPase of Yoshida sarcoma membrane fragments inactivated by P6 protein could be reconstituted by the addition of phosphatidylserine and phosphatidic acid. It is conceivable that lysis of cells by the P6 protein may be due to an imbalance of K-+ and Na-+ in the cell which leads to swelling and disintegration of the membrane structure. Observations indicate that the P6 protein combines with membrane constituents of susceptible cells. The overall evidence suggests that both the specificity of its protein structure and the highly basic nature of the P6 protein are factors which enable it to compete with the lipid moiety maintaining the (Na-++k-+)-ATPase of the susceptible cells in proper conformation for activity.     

An Alteration in ELMOD3, an Arl2 GTPase-Activating Protein,Is Associated with Hearing Impairment in Humans

Exome sequencing coupled with homozygosity mapping was used to identify a transition mutation (c.794T>C; p.Leu265Ser) in ELMOD3 at the DFNB88 locus that is associated with nonsyndromic deafness in a large Pakistani family, PKDF468. The affected individuals of this family exhibited pre-lingual, severe-to-profound degrees of mixed hearing loss. ELMOD3 belongs to the engulfment and cell motility (ELMO) family, which consists of six paralogs in mammals. Several members of the ELMO family have been shown to regulate a subset of GTPases within the Ras superfamily. However, ELMOD3 is a largely uncharacterized protein that has no previously known biochemical activities. We found that in rodents, within the sensory epithelia of the inner ear, ELMOD3 appears most pronounced in the stereocilia of cochlear hair cells. Fluorescently tagged ELMOD3 co-localized with the actin cytoskeleton in MDCK cells and actin-based microvilli of LLC-PK1-CL4 epithelial cells. The p.Leu265Ser mutation in the ELMO domain impaired each of these activities. Super-resolution imaging revealed instances of close association of ELMOD3 with actin at the plasma membrane of MDCK cells. Furthermore, recombinant human GST-ELMOD3 exhibited GTPase activating protein (GAP) activity against the Arl2 GTPase, which was completely abolished by the p.Leu265Ser mutation. Collectively, our data provide the first insights into the expression and biochemical properties of ELMOD3 and highlight its functional links to sound perception and actin cytoskeleton.     

Vesicular trafficking–related proteins as the potential therapeutic target for breast cancer

Protoplasma - Vesicular trafficking between endoplasmic reticulum and Golgi plays a major role in the growth and proliferation of breast cancer cells. Various proteins regulate this ER-Golgi...     

Supplementation of Taurine Insulates Against Oxidative Stress,Confers Neuroprotection and Attenuates Memory Impairment in Noise Stress Exposed Male Wistar Rats

Noise has always been an important environmental factor that induces health problems in the general population. Due to ever increasing noise pollution, humans are facing multiple auditory and non-auditory problems including neuropsychiatric disorders. In modern day life it is impossible to avoid noise due to the rapid industrialization of society. Continuous exposure to noise stress creates a disturbance in brain function which may lead to memory disorder. Therefore, it is necessary to find preventive measures to reduce the deleterious effects of noise exposure. Supplementation of taurine, a semi essential amino acid, is reported to alleviate psychiatric disorders. In this study noise-exposed (100 db; 3 h daily for 15 days) rats were supplemented with taurine at a dose of 100 mg/kg for 15 days. Spatial and recognition memory was assessed using the Morris water maze and novel object recognition task, respectively. Results of this study showed a reversal of noise-induced memory impairment in rats. The derangements of catecholaminergic and serotonergic levels in the hippocampus and altered brain antioxidant enzyme activity due to noise exposure were also restored by taurine administration. This study highlights the importance of taurine supplementation to mitigate noise-induced impaired memory via normalizing the neurochemical functions and reducing oxidative stress in rat brain.

     

Aluminium oxide nanoparticles inhibit EPS production,adhesion and biofilm formation by multidrug resistant Acinetobacter baumannii

Abstract

Acinetobacter baumannii is a biofilm forming multidrug resistant (MDR) pathogen responsible for respiratory tract infections. In this study, aluminium oxide nanoparticles (Al₂O₃ NPs) were synthesized and characterized by TEM and EDX and shown to be spherical shaped nanoparticles with a diameter < 10?nm. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) for the Al₂O₃ NPs ranged between 125 and 1,000?µg ml^?1. Exposure to NPs caused cellular membrane disruption, indicated by an increase in cellular leakage of the contents. Biofilm inhibition was 11.64 to 70.2%, whereas attachment of bacteria to polystyrene surfaces was reduced to 48.8 to 51.9% in the presence of NPs. Nanoparticles also reduced extracellular polymeric substance production and the biomass of established biofilms. The data revealed the non-toxic nature of Al₂O₃ NPs up to a concentrations of 120?µg ml^?1 in HeLa cell lines. These results demonstrate an effective and safer use of Al₂O₃ NPs against the MDR A. baumannii by targeting biofilm formation, adhesion and EPS production.     

Enhanced Expression of Glia Maturation Factor Correlates with Glial Activation in the Brain of Triple Transgenic Alzheimer’s Disease Mice

We previously demonstrated that glia maturation factor (GMF), a brain specific protein, isolated, sequenced and cloned in our laboratory, induce expression of proinflammatory cytokines and chemokines in the central nervous system. We also reported that the up-regulation of GMF in astrocytes leads to the destruction of neurons suggesting a novel pathway of GMF-mediated cytotoxicity of brain cells, and implicated its involvement in the pathogenesis of inflammatory neurodegenerative diseases. In the present study, we examined the expressions of GMF in triple-transgenic Alzheimer’s disease (3xTg-AD) mice. Our results show a 13-fold up-regulation of GMF and 8–12-fold up-regulation of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, interferon gamma (IFN-γ), and chemokine (C–C motif) ligand 2 (CCL2) and C–X–C motif chemokine 10 (CXCL10/IP-10) mRNA as determined by quantitative real-time RT-PCR in the brain of 3xTg-AD mice as compared to non-transgenic (Non-Tg) mice. In conclusion, the increase in GMF and cytokine/chemokine expression was correlated with reactive glial fibrillary acidic protein positive astrocytes and ionized calcium binding adaptor molecule 1 (Iba-1)-positive microglia in 3xTg-AD mice.