Intracellular inactivation

Infections caused by antibiotic-resistant bacteria expose an important risk to human health around the world. These bacteria are very resistant to traditional antibiotics owing to acquired resistance, inadequate diffusion and intracellular inactivation. Therefore, the development of novel antimicrobial materials with high protection and antibacterial activity, which lack bacterial resistance, is critical. 

The picture that emerges from this evidence is that intracellular inactivation events suffered by the transfecting DNA prevent replication of the input DNA. Genetic recombination between several input genomes must... 

Green, D. M. Intracellular inactivation of infective SP82 bacteriophage DNA. J. molec. Biol. 22, 1-13 (1966a). 

Smooth muscle contractions are subject to the actions of hormones and related agents. As shown in Figure 17.32, binding of the hormone epinephrine to smooth muscle receptors activates an intracellular adenylyl cyclase reaction that produces cyclic AMP (cAMP). The cAMP serves to activate a protein kinase that phosphorylates the myosin light chain kinase. The phosphorylated MLCK has a lower affinity for the Ca -calmodulin complex and thus is physiologically inactive. Reversal of this inactivation occurs via myosin light chain kinase phosphatase. 

An increase in [Na+]j can also regulate the Na+/Ca2+ exchanger. In particular, when intracellular Na+ increases, it binds to the transport site of the exchanger molecule, and after this Na+ influx, an inactivation process of the exchanger occurs. This inactivation process, very similar to the phenomenon occurring in voltage-dependent ionic channels, is named... 

Na+-dependent inactivation. There is a sequence of 20-aminoacids (219-23 8), located in the intracellular f loop near the membrane lipid interface, that seems to be involved in the Na+-dependent inactivation. This autoinhibitory 20-aminoacid sequence might interact with another portion of the f loop (562-679) producing NCX inhibition. In accordance with this view, the synthetic peptide provided with the same sequence of XIP region blocks NCX activity. 

The transporters for 5HT, noradrenaline and dopamine, biogenic monoamines, are genetically related, exist as single isoforms and are expressed on the surface of nerve cells, which use monoamines as (or convert them into) their cognate neurotransmitter. The single-isoform monoamine transporters fulfil all three fundamental functions (reuptake, limiting synaptic transmission, and control of the extracellular neurotransmitter concentration). Inactivation of DAT, NET, or SERT results in an increased extracellular lifetime and level of monoamine neurotransmitter, but decreased intracellular storage and evoked release (Fig. 3). 

Fig. 9.1 Schematic representation of possible mechanisms of resistance in Gram-negative and Gram-positive bacteria. 1, antibiotic-inactivating enzymes 2, antibiotic efflux proteins 3, alteration or duplication of intracellular targets 4, alteration of the cell membrane reducing antibiotic uptake 5, alterations in porins or lipopolysaccharide reducing antibiotic uptake or binding.

Plasmid- ortransposon-mediated resistance occurs by inactivation ofthe antibiotic. Fosfomycin is combined with glutathione intracellularly to produce a compound lacking in antibacterial activity. The gene encoding the enzyme catalysing this reaction has been designated/or-r. 

Fig. 5. Proposed topology of K channel subunits inserted into the membrane. COO carboxy-terminal. The proposed membrane-spanning segments SI-S6 in the core region of channel proteins are displayed linearly. H5 may be part of the K channel pore. The amino-terminal inactivation gate is symbolized by a positively charged ball which could occlude the pore region. The extracellular side is thought to be at top and the intracellular side at bottom.

Hyslop, P.A., Hinshaw, D.B., Halsey, W.A., Schraufttatter, I.U., Sauerheber, RD., Spragg, RG., Jackson, J.H. and Cochrane, C.G. (1988). Mechanisms of oxidant-mediated cell injury. The glycolytic and mitochondrial pathways of ADP phosphorylation as major intracellular targets inactivated by hydrogen peroxide. J. Biol. Chem. 263, 1665-1671. 

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