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  • br Other mechanisms In vitamin

    2021-10-13


    Other mechanisms In vitamin B6 deficiency, antibody production may be indirectly impaired [38]. Grindley et al. [4] showed that high dietary intake of vitamin B6 (74.3 mg PN/kg diet) suppresses herpes simplex virus type 2 transformed cell-induced tumor growth and enhances immune status compared with a 1.2 mg PN/kg diet in BALB/c mice. The preventive effect of vitamin B6 against colon tumorigenesis might be in part mediated through alteration in immune function. Vitamin B6 plays an important role in homocysteine metabolism serving a critical role in homocysteine catabolism. In the process of homocysteine catabolism, cysteine, a main component for the synthesis of glutathione, is generated. Gutathione serves as an important cofactor of the glutathione S-transferase and glutathione peroxidase, which function in the detoxification of many toxic or carcinogenic compounds. Vitamin B6 also facilitates the transfer of a methyl group to tetrahydrofolate, yeilding 5, 10-methylenetetrahydrofolate needed for reactions generating thymidylate and purines. Thus, disruption of these reactions may lead to imbalances in methyl groups required for methylation process, including DNA methylation. Altered DNA methylation has been observed in tumors at several sites [39], [40]. The alterations of these metabolisms by dietary vitamin B6 might lead to the antitumor effect of vitamin B6.
    Conclusions This review focused on the preventive effect of dietary vitamin B6 against colon tumorigenesis. Its antitumor effect in the mice received AOM appeared to be evident by moderate dietary levels of vitamin B6 being close to the recommended level in the diet. Recent epidemiological studies also support an inverse association between vitamin B6 intake and colon cancer risk. The preventive effect of vitamin B6 against colon tumorigenesis in mice appears to be mediated through suppressing cell hyperproliferation, oxidative stress, and NO synthesis in the colon. In vitro studies have further provided evidence for antiangiogenic effect of vitamin B6. These studies emphasize the importance of vitamin B6 as an antitumor factor [28].
    Anthrax is a zoonotic contagious fatal disease caused by (). It is primarily a disease of herbivores, but all mammals, including humans, are susceptible hosts. In 2001, the bioterrorists intentionally released anthrax in the United States and resulted in 11 cases of inhalational disease with an attendant mortality rate of 45% . is a rod-shaped, gram-positive, and spore-forming bacterium. The infection is initiated by the entry of spores into the host body through a minor abrasion, an insect bite, or by eating contaminated meat or inhaling airborne spores , . Therefore the manipulation of the bacteria needs biosafety level 3 facilities. The main virulence factors of include poly--glutamic smad inhibitor capsule and anthrax lethal toxin (LeTx). LeTx plays a key role in anthrax pathogenesis both in the early stages of the disease and throughout the disease progression, while the poly--glutamic capsule protects from being killed by macrophages , . LeTx is a binary AB toxin composed of three secreted proteins protective antigen (PA, 83kDa), lethal factor (LF, 90kDa), and edema toxin (EF, 89kDa). PA, the B part of toxin, plus A part LF calls lethal toxin, while PA when combined with another A part EF forms edema toxin , , . Because LeTx treatments could reproduce most symptoms of infection, LeTx has been utilized in studying anthrax pathogenesis , and treatment . Since antimicrobials only target replicating organisms, thus leaving bacterial toxins to cause unchecked physiological derangements in the host, novel approaches that target the cytotoxic effects of anthrax exotoxins are pursued including the development of new chemicals , , use of antibodies , and toxin mutants , , . LF is a Zn-endopeptidase specific for the MAPK-kinase family of proteins and a key virulence factor for since mouse death was seen in the absence of edema factor, but not in the absence of lethal factor . It causes cell death by preventing the association of MAPKK1 with its substrate and inhibits the MAPK signal transduction pathways including ERK (extracellular signal-regulated kinase), p38 MAPK and JNK (c-Jun N-terminal kinase) pathways , . Therefore, inhibition of this proteolytic-based LF toxemia could eventually provide a therapeutic value in combination with an antibiotic treatment during and immediately after an active anthrax infection . As mentioned previously, biologically active LF might be purified from culture . However, the hazardous restricts the ordinary laboratories to perform such purification. Although LF has been expressed in , , , , the conventional purification strategies involve complicate purification procedure (e.g., gel filtration, Mono Q FPLC, anion exchange) and tedious changes of buffers and are not suitable for a protease like LT which is easily degraded. Thus a simple and straightforward method to obtain high quality recombinant LF (rLF) or its mutants is needed. To this end, several strategies have been utilized, such as fusion of the LF gene to the leader sequence of outer membrane protein OmpA so that the rLF can be translocated into the periplasm and its degradation was decreased, or fusion of LF to a His Tag to facilitate protein purification by one-step nickel affinity column , , . However, it is necessary for these methods to remove unbeneficial reagents present in buffers by dialysis or cleave the fused tags by additional steps. In this study, we expressed rLF as a fusion protein with GST-tag (GST-rLF) in and the GST-tag was cleaved through a single affinity purification step which used only phosphate-buffered saline (PBS) buffer in the whole purification procedure. At the same time, a novel rLF mutant (rLFm-Y236F) was obtained. The cytotoxicity analysis demonstrated that the purified rLF was fully functional, while the rLFm-Y236F lost its activity. The purification method developed in this study combined the new mutant might provide useful tools for the research in anthrax-mediated pathogenesis and anthrax therapy.