- MeSH
- alergie na pšenici imunologie MeSH
- dieta MeSH
- imunologické testy MeSH
- lidé MeSH
- mléčné bílkoviny imunologie škodlivé účinky MeSH
- mléko imunologie MeSH
- nemoci střev imunologie MeSH
- nesnášenlivost laktózy imunologie MeSH
- obezita imunologie MeSH
- permeabilita buněčné membrány imunologie MeSH
- potravinová alergie * imunologie MeSH
- potravinová intolerance * imunologie MeSH
- pšenice imunologie škodlivé účinky MeSH
- Check Tag
- lidé MeSH
The lipid components of pathogen cell membranes have been considered as a poor pharmacological target, due to their universal distribution and apparent homogeneity throughout living organisms. Among the rare exceptions to this view one could mention polyene antibiotics such as amphotericin, or peptide antibiotics such as the polymyxins and the gramicidins. In the last two decades, however, the above notion has been challenged by two main lines of discovery; first, natural antimicrobial peptides (AMPs) that kill pathogens by interaction with phospholipids and membrane permeabilization, and secondly, cell-penetrating peptides (CPPs), capable of introducing into cells a variety of cargoes in the absence of specific receptors, again by interaction at some point with membrane phospholipids. For both AMPs and CPPs, the pharmacological proof-of-concept has been successfully demonstrated, and promising applications as nanobiotechnological tools have been envisaged though not hitherto materialized in clinical settings. In this review we briefly examine the pros and cons of these two classes of therapeutic agents, as well as strategies aimed at rationalizing and expanding their potentiality.
- MeSH
- antibiotická rezistence genetika imunologie MeSH
- financování organizované MeSH
- infekční nemoci farmakoterapie MeSH
- kationické antimikrobiální peptidy genetika účinky léků MeSH
- lidé MeSH
- lipopolysacharidy biosyntéza MeSH
- mikrochemie metody trendy MeSH
- peptidy genetika metabolismus účinky léků MeSH
- permeabilita buněčné membrány genetika imunologie účinky léků MeSH
- rostliny MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
The strategies used by living organisms to survive under low and freezing temperatures reveal the extraordinary adaptability of life on Earth. Understanding the molecular mechanisms underlying cold adaptation and freezing survival will provide new insights into the existing relationships between living organisms and their environment, and the possibility of developing multiple biotechnological applications. In the case of plants, the use of classical genetic and new "omics" approaches is allowing to the identification of new elements involved in regulating the cold acclimation response. The challenge ahead is to determine temperature-perception molecules and mechanisms, to uncover new internodes of multiple responses, and to integrate the regulation not only at the transcriptome but also at proteome and metabolome levels. Attaining these goals will significantly contribute global understanding the adaptive strategies plants have evolved to cope with hostile environmental conditions, and to the development biotechnological strategies to improve crop tolerance to freezing and other important abiotic stresses.
- MeSH
- adaptorové proteiny signální transdukční genetika imunologie MeSH
- aklimatizace fyziologie genetika imunologie MeSH
- Arabidopsis cytologie genetika imunologie MeSH
- biologická adaptace fyziologie genetika imunologie MeSH
- biotechnologie metody trendy MeSH
- cytosol chemie metabolismus MeSH
- financování organizované MeSH
- fyziologická adaptace fyziologie genetika imunologie MeSH
- metabolomika metody MeSH
- molekulární biologie metody MeSH
- nízká teplota škodlivé účinky MeSH
- permeabilita buněčné membrány fyziologie genetika imunologie MeSH
- proteomika metody MeSH
- regulace genové exprese genetika imunologie MeSH
- rostliny MeSH
- Publikační typ
- přehledy MeSH
Bordetella adenylate cyclase (AC) toxin-hemolysin (CyaA) targets myeloid phagocytes expressing the alphaMbeta2 integrin (CD11b/CD18) and delivers into their cytosol an AC enzyme that converts ATP into cyclic AMP (cAMP). In parallel, CyaA acts as a hemolysin, forming small membrane pores. Using specific mutations, we dissected the contributions of the two activities to cytolytic potency of CyaA on J774A.1 murine monocytes. The capacity of AC to penetrate cells and deplete cytosolic ATP was essential for promoting lysis and the enzymatically inactive but fully hemolytic CyaA-AC- toxoid exhibited a 15-fold-lower cytolytic capacity on J774A.1 cells than intact CyaA. Moreover, a two- or fourfold drop of specific hemolytic activity of the CyaA-E570Q and CyaA-E581P mutants was overpowered by an intact capacity to dissipate cytosolic ATP into cAMP, allowing the less hemolytic proteins to promote lysis of J774A.1 cells as efficiently as intact CyaA. However, an increased hemolytic activity, due to lysine substitutions of glutamates 509, 516, and 581 in the pore-forming domain, conferred on AC- toxoids a correspondingly enhanced cytolytic potency. Moreover, a threefold increase in hemolytic activity could override a fourfold drop in capacity to convert cellular ATP to cAMP, conferring on the CyaA-E581K construct an overall twofold increased cytolytic potency. Hence, although appearing auxiliary in cytolytic action of the toxin on nucleated cells, the pore-forming activity can synergize with ATP-depleting activity of the cell-invasive AC enzyme and complement its action toward maximal cytotoxicity.
- MeSH
- adenosintrifosfát metabolismus MeSH
- adenylátcyklasový toxin toxicita MeSH
- AMP cyklický metabolismus MeSH
- antigeny CD11b metabolismus MeSH
- antigeny CD18 metabolismus MeSH
- Bordetella pertussis enzymologie imunologie MeSH
- buněčná smrt imunologie MeSH
- buněčné linie MeSH
- CHO buňky MeSH
- Cricetulus MeSH
- cytotoxicita imunologická MeSH
- erytrocyty metabolismus MeSH
- financování organizované MeSH
- křečci praví MeSH
- monocyty enzymologie imunologie MeSH
- myši MeSH
- ovce MeSH
- permeabilita buněčné membrány imunologie MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- myši MeSH
- zvířata MeSH
[1st ed.] XXI,766 s. : tab.,fot., přeruš.lit., věc. rejstř. ; 28 cm
- MeSH
- alergologie a imunologie MeSH
- imunologické faktory fyziologie MeSH
- permeabilita buněčné membrány imunologie MeSH
- sliznice patofyziologie fyziologie imunologie MeSH
- Publikační typ
- příručky MeSH
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- alergologie a imunologie
- fyziologie
- MeSH
- buněčná membrána * fyziologie imunologie MeSH
- fosfolipidy fyziologie imunologie MeSH
- imunita fyziologie imunologie MeSH
- ligandy MeSH
- lymfocyty * fyziologie imunologie MeSH
- membránové proteiny MeSH
- modely imunologické MeSH
- permeabilita buněčné membrány fyziologie imunologie MeSH
- receptory buněčného povrchu MeSH
- savci MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- Bacteria MeSH
- bakteriologické techniky metody trendy využití MeSH
- bakteriologie trendy MeSH
- fosfolipidy izolace a purifikace klasifikace MeSH
- glykolipidy izolace a purifikace MeSH
- lidé MeSH
- lipidy * izolace a purifikace klasifikace MeSH
- permeabilita buněčné membrány * fyziologie imunologie účinky léků MeSH
- Staphylococcaceae enzymologie izolace a purifikace klasifikace MeSH
- statistika jako téma MeSH
- Check Tag
- lidé MeSH