Biosynthesis of polymyxin by Bacillus polymyxa. II. On the nature and interaction of the multienzyme complex with the end product polymyxin

The interaction of polymyxin with the producer organism Bacillus polymyxa has been shown to be at the level of membranes, resulting in an enhancement of the activities of its own biosynthetic enzymes. This enhancement has been shown to be due to the solubilization of the membrane-associated multienzyme complex by polymyxin in a specific manner. The relevance of this physiological feature was also indicated by the appearance of the soluble multienzyme complex activity only in cells, which synthesize maximal amounts of polymyxin. Purification of the polymyxin released multienzyme complex from the membranes and the soluble form of the complex from the stationary phase cells has revealed several similarities between them. Both contain two major fractions of the molecular weights of 300,000 and 170,000, harboring all the polymyxin component amino acid-activating enzymes. Their multisubunit nature was established by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. Using mutants blocked in sporulation and/or antibiotic synthesis, it was shown that the interaction of polymyxin with the producer organism was inoperative when antibiotic production was curtailed. This interaction has been suggested as one of the early sporulation-specific phenemenon.     

Influence of monosaccharides on the fibrillogenesis of type I collagen

The in vitro self-assembly of Type I rat tail tendon collagen in the presence of monosaccharides was studied turbidimetrically. D(+)glucose and D(+)mannose delayed fibril formation significantly while D(-)fructose showed no variation. The effect of glucose was concentration dependent. Binding of glucose during fibrillogenesis was shown by the incorporation of [14C]glucose and also by SDS-polyacrylamide slab gel electrophoresis of the product. The results indicate that in vitro nonenzymatic glycosylation can take place in the short duration required for fibril formation.     

Ascorbic acid is a key participant during the interactions between chloroplasts and mitochondria to optimize photosynthesis and protect against photoinhibition

The possible role of L-ascorbate (AsA) as a biochemical signal during the interactions between photosynthesis and respiration was examined in leaf discs of Arabidopsis thaliana. AsA content was either decreased as in AsA-deficient vtc1 mutants or increased by treatment with L-galactono-1, 4-lactone (L-GalL, a precursor of AsA; EC 1.3.2.3). In mutants, photosynthesis was extremely sensitive to both antimycin A (inhibitor of the cytochrome c oxidase pathway [COX pathway]) and salicylhydroxamic acid (SHAM, inhibitor of the alternative pathway [AOX pathway]), particularly at high light conditions. Mitochondrial inhibitors lowered the ratio of reduced AsA to total AsA, at high light, indicating oxidative stress in leaf discs. Elevation of AsA by L-GalL decreased the sensitivity of photosynthesis at high light to antimycin A or SHAM, sustained photosynthesis at supraoptimal light and relieved the extent of photoinhibition. High ratios of reduced AsA to total AsA in L-GalL-treated leaf discs suggests that L-GalL lowers oxidative stress. The protection by L-GalL of photosynthesis against the mitochondrial inhibitors and photoinhibition was quite pronounced in vtc1 mutants. Our results suggest that the levels and redox state of AsA modify the pattern of modulation of photosynthesis by mitochondrial metabolism. The extent of the AOX pathway as a percentage of the total respiration in Arabidopsis mesophyll protoplasts was much higher in vtc1 than in wild type. We suggest that the role of AsA becomes pronounced at high light and/or when the AOX pathway is inhibited. While acknowledging the importance of the COX pathway, we hypothesize that AsA and the AOX pathway may complement each other to protect photosynthesis against photoinhibition.     

Modulation of TCA cycle enzymes and electron transport chain systems in experimental lung cancer

The modulatory effect of Withania somnifera along with paclitaxel on tricarboxylic acid (TCA) cycle key enzymes and electron transport chain complexes were investigated against lung cancer induced by benzo(a)pyrene in Swiss albino mice. Decreased activities of TCA cycle key enzymes such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) in lung cancer bearing animals were observed. Upon W. somnifera along with paclitaxel administration the above biochemical changes were inclined towards normal control animal values. Activities of mitochondrial enzymes and electron transport complexes were analyzed in the experimental groups to determine the efficiency of energy production. This study further confirms the chemotherapeutic effect of W. somnifera along with paclitaxel which is found to be more effective in the treatment of lung cancer. Thus these results are consistent with our hypothesis that the combination chemotherapy of W. somnifera along with paclitaxel as a promising chemotherapeutic agent.     

Therapeutic effect of paclitaxel and propolis on lipid peroxidation and antioxidant system in 7,12 dimethyl benz(a)anthracene-induced breast cancer in female Sprague Dawley rats

Breast cancer is one of the most common cancers in women of developed and developing countries. The optimum management of which requires a multidisciplinary approach including the use of certain biochemical and molecular markers. The effect of propolis along with paclitaxel on 7,12 dimethyl benz(a)anthracene (DMBA) induced experimental breast cancer was investigated in female Sprague Dawley rats. Female Sprague Dawley rats were divided into five groups of six animals each. Group I served as normal control animal. Group II animals received DMBA (20 mg in 0.5 ml sunflower oil and 0.5 ml of saline) i.p. to develop mammary tumor by the end of 90 days. Group III were breast cancer animals treated with 33 mg paclitaxel/kg body weight (bw) weekly once for 4 weeks. Group IV were breast cancer-bearing animals treated with 50 mg propolis/kg bw for 30 days. Group V were breast cancer-bearing animals treated with both paclitaxel and propolis as mentioned above. Administration of paclitaxel and propolis effectively suppressed breast cancer, which is revealed by the decrease in the extent of lipid peroxidation (LPO) with concomitant increase in the activities of enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) and non-enzymic antioxidants (reduced glutathione (GSH), Vitamin C and Vitamin E) levels when compared to breast cancer-bearing animals treated with either paclitaxel or propolis alone. From our results, we conclude that propolis is a potent antioxidant and, when given in combination with paclitaxel, offers maximum protection against DMBA induced mammary carcinogenesis.     

Sphingosine-1-phosphate lyase in immunity and cancer: silencing the siren

Sphingosine-1-phosphate (S1P) is a bioactive lipid that promotes cell survival, proliferation and migration, platelet aggregation, mediates ischemic preconditioning, and is essential for angiogenesis and lymphocyte trafficking. Sphingosine-1-phosphate lyase (SPL) is the enzyme responsible for the irreversible degradation of S1P and is, thus, in a strategic position to regulate these same processes by removing available S1P signaling pools, that is, silencing the siren. In fact, recent studies have implicated SPL in the regulation of immunity, cancer surveillance and other physiological processes. Here, we summarize the current understanding of SPL function and regulation, and discuss how SPL might facilitate cancer chemoprevention and serve as a target for modulation of immune responses in transplantation settings and in the treatment of autoimmune disease.     

Synthesis of Amido Sulfonamido Heteroaromatics Under Ultrasonication and Their Antimicrobial Activity

A convenient and facile methodology for N‐sulfonylation of heteroaryl amines with ethyl chlorosulfonylacetate in the presence of dispersed sodium in THF under ultrasonication is reported. The corresponding heteroaryl sulfonamido esters are directly condensed with heteroaryl amines to get amido sulfonamido heteroaromatics in the presence of a mild base in THF under ultrasonication. Utilization of easy reaction conditions, shorter reaction times, and isolation of products in high yields under ultrasonication make this process as economically viable. The compounds 12c , 12d , 12f and 13f are potential antibacterial agents against B. subtilis and the compounds 12f , 13c and 13f are potential antifungal agents against A. niger.     

Amelioration of alcohol-induced oxidative stress by Emblica officinalis (amla) in rats

The present study was aimed at investigating the ameliorative effect of Emblica (Phyllanthus Emblica L) fruit extract (EFE) against alcohol-induced oxidative changes in plasma biochemical profile in rats. Alcohol administration (5 g/kg body wt/day) for 60 days resulted in significantly (P<0.05) higher levels of plasma nitrite/nitrate (NOx), total bilirubin, creatinine, and abnormalities in lipid and lipoproteins. Moreover, alcohol receiving rats showed significantly (P<0.05) lowered plasma total protein, albumin/globulin (A/G) ratio and uric acid, with no significant change in glucose level. The EFE administration (250 mg/kg body wt/day) to alcohol-administered rats significantly modulated plasma lipids and lipoprotein patterns and also decreased nitrite/nitrate, total bilirubin and creatinine levels. EFE administration to alcohol receiving rats showed a significant (P<0.05) increase in plasma total protein, A/G ratio and uric acid levels. Total cholesterol (r = 0.466), triglycerides (r = 0.574), VLDL-C (r = 0.578), LDL-C (r = 0.225) and total bilirubin (r = 0.419) showed a stronger positive correlation with that of NOx in alcohol-treated rats. The concentration of nitric oxide (NOx) was negatively correlated with HDL-C (r = -0.285) and uric acid (r = 0.392) in alcohol-treated rats. The amelioration of alcohol-induced oxidative stress might be due to the combined effect of phytophenols, such as tannins and flavonoid compounds and vitamin C.     

Human tumor necrosis factor alpha-induced protein eight-like 1 exhibited potent anti-tumor effect through modulation of proliferation,survival, migration and invasion of lung cancer cells

Molecular and Cellular Biochemistry - Lung cancer represents one of the most prevalent neoplasms across the globe. Tobacco smoking, exposure to different occupational and environmental carcinogens,...     

Sorcin a Potential Molecular Target for Cancer Therapy

Sorcin (Soluble resistance related calcium binding protein) is a small soluble penta EF family (PEF) of calcium (Ca²⁺) binding protein (22,000 Da). It has been reported to play crucial roles in the regulation of calcium homeostasis, apoptosis, vesicle trafficking, cancer development, and multidrug resistance (MDR). Overexpression of sorcin has been reported to be associated with different cancers such as breast cancer, colorectal cancer, gastric cancer, leukemia, lung cancer, nasopharyngeal cancer, ovarian cancer, etc. Essentially, expression of sorcin has been found to be elevated in cancer cells as compared to normal cells, indicating that it has prominent role in cancer. Moreover, sorcin was found to be the regulator of various proteins that has an association with carcinogenesis including NF-κB, STAT3, Akt, ERK1/2, VEGF, MMPs, caspases, etc. Sorcin was also found to regulate apoptosis, as silencing of the same resulted in increased levels of proapoptotic genes and induced mitochondrial apoptotic pathway in cancer. Interestingly, mutations in the sorcin gene have been closely linked with poor overall survival in bladder cancer, brain lower-grade glioma, glioblastoma, glioblastoma multiforme, kidney renal clear cell carcinoma, and stomach adenocarcinoma. Additionally, overexpression of sorcin was also found to induce MDR against different chemotherapeutic drugs. All these findings mark the importance of sorcin in cancer development and MDR. Therefore, there is urgent need to explore the functional mechanism of sorcin and to analyze whether silencing of sorcin would able to chemosensitize MDR cells. The current review summarizes the structure, expression, and functions of sorcin and its importance in the regulation of various malignancies and MDR.