That alter cell membrane function

TOXICANTS THAT ALTER CELL MEMBRANE FUNCTION... 

Mechanisms by which ozone might interfere with bactericidal function include an alteration in cell-membrane function that produces a loss in phagocytic ability and is perhaps mediated by lipid peroxides and a decrease in the ability of veolar macrophages to kill phagocytized bacteria. Leukocytes in general appear to have a multiplicity of mechanisms for destroying ingested bacteria. 

The importance of lipid mesomorphic tendencies on cell membrane function has also been suggested by studies in which the lipid composition of cells has been varied. Such experiments are problematic because cells maintain regulatory apparatus that makes it difficult to alter the biomembrane lipid composition in a controlled manner. Furthermore, for eukaryotes, it is hard to obtain the pure membrane fractions of a single organelle membrane such as are required for meaningful determinations of the lipid compositions of particular membranes. In the case of bacteria, it is difficult to obtain pure plasma membrane fractions without cell wall contamination. However, my-coplasmas with only a single plasma membrane allow unambiguous determination of the overall plasma membrane composition. 

Allelopathic inhibition of mineral uptake results from alteration of cellular membrane functions in plant roots. Evidence that allelochemicals alter mineral absorption comes from studies showing changes in mineral concentration in plants that were grown in association with other plants, with debris from other plants, with leachates from other plants, or with specific allelochemicals. More conclusive experiments have shown that specific allelochemicals (phenolic acids and flavonoids) inhibit mineral absorption by excised plant roots. The physiological mechanism of action of these allelochemicals involves the disruption of normal membrane functions in plant cells. These allelochemicals can depolarize the electrical potential difference across membranes, a primary driving force for active absorption of mineral ions. Allelochemicals can also decrease the ATP content of cells by inhibiting electron transport and oxidative phosphorylation, which are two functions of mitochondrial membranes. In addition, allelochemicals can alter the permeability of membranes to mineral ions. Thus, lipophilic allelochemicals can alter mineral absorption by several mechanisms as the chemicals partition into or move through cellular membranes. Which mechanism predominates may depend upon the particular allelochemical, its concentration, and environmental conditions (especially pH). 

Before the first indication of the existence of cannabinoid receptors, the prevailing theory on the mechanism of cannabinoid activity was that cannabinoids exert their effects by nonspecific interactions with cell membrane lipids (Makriyannis, 1990). Such interactions can increase the membrane fluidity, perturb the lipid bilayer and concomitantly alter the function of membrane-associated proteins (Loh, 1980). A plethora of experimental evidence suggests that cannabinoids interact with membrane lipids and modify the properties of membranes. However, the relevance of these phenomena to biological activities is still only, at best, correlative. An important conundrum associated with the membrane theories of cannabinoid activity is uncertainty over whether cannabinoids can achieve in vivo membrane concentrations comparable to the relatively high concentrations used in in vitro biophysical studies (Makriyannis, 1995). It may be possible that local high concentrations are attainable under certain physiological circumstances, and, if so, some of the cannabinoid activities may indeed be mediated through membrane perturbation. 

In some human studies where clinical chemistry measurements but no renal biopsies were performed, the only parameter of renal function shown to be affected was an increase in the levels of NAG in the urine. NAG is a lysosomal enzyme present in renal tubular cells that has been shown to be a sensitive indicator of early subclinical renal tubular disease. The mechanism by which lead affects the release of NAG from renal tubular cells is not known, but it is suggested that lead could attach to kidney cell membranes and alter membrane permeability (Chia et al. 1994). 

The neurotransmitters of the ANS and the circulating catecholamines bind to specific receptors on the cell membranes of effector tissue. Each receptor is coupled to a G protein also embedded within the plasma membrane. Receptor stimulation causes activation of the G protein and formation of an intracellular chemical, the second messenger. (The neurotransmitter molecule, which cannot enter the cell, is the first messenger.) The function of intracellular second messenger molecules is to elicit tissue-specific biochemical events within the cell that alter the cell s activity. In this way, a given neurotransmitter may stimulate the same type of receptor on two different types of tissue and cause two different responses due to the presence of different biochemical pathways within each tissue. 

The number of channels synthesized, processed, and trafficked to the apical membrane and rate of CFTR internalization at the apical membrane determine the cell surface density. Mutations in CFTR that alter one or more of these parameters decrease total CFTR-mediated anion flux and impair epithelial cell function. 

During the last ten years, it has become apparent that calcium-dependent papain-like peptidases called calpains (EC 3.4.22.17) represent an important intracellular nonlysosomal enzyme system [35][36], These enzymes show limited proteolytic activity at neutral pH and are present in virtually every eukaryotic cell type. They have been found to function in specific proteolytic events that alter intracellular metabolism and structure, rather than in general turnover of intracellular proteins. Calpains are composed of two nonidentical subunits, each of which contains functional calcium-binding sites. Two types of calpains, i.e., /i-calpain and m-calpain (formerly calpain I and calpain II, respectively), have been identified that differ in their Ca2+ requirement for activation. The activity of calpains is regulated by intracellular Ca2+ levels. At elevated cytoplasmic calcium concentrations, the precursor procal-pain associates with the inner surface of the cell membrane. This interaction seems to trigger autoproteolysis of procalpain, and active calpain is released into the cytoplasm [37]. 

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