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At least 19 recordsLinked to original sources

Relationship of phospholipid hexagonal phases to biological phenomena.

Phospholipid bilayers can undergo morphological rearrangements to other phases. The formation of one of these nonbilayer phases, the hexagonal phase, is preceded by an increase in the hydrophobicity of the bilayer surface and a destabilization of the bilayer structure. Certain membrane additives promote, while others inhibit, the formation of the hexagonal phase. Many of the molecular features that determine this phase preference are understood. Some of the properties of membranes are modulated by agents that affect the relative stability of the bilayer and hexagonal phases. Addition of bilayer stabilizers to a membrane decreases its fusogenic behaviour. One such bilayer stabilizer is cholesterol sulfate, which may function physiologically to inhibit the fusion of sperm cells. Several antiviral agents are also found to be bilayer stabilizers and some have been shown to inhibit membrane fusion phenomena. Another biological property that is modulated in a predictable manner by agents which affect the bilayer-hexagonal phase equilibrium is insulin-promoted glucose uptake in adipocytes. Bilayer stabilizers inhibit this process showing that the effects of insulin can be modulated by the bulk biophysical properties of the membrane. The activity of a number of membrane-bound enzymes is also lowered by bilayer stabilizers. Neutral and zwitterionic bilayer stabilizers are inhibitors of protein kinase C. Thus, the alteration of the bilayer-hexagonal phase transition by drugs may provide a useful parameter for predicting their effects on biological membranes.

Adipose Tissue↗

Exploring the relationship between the inhibition of gap junctional intercellular communication and other biological phenomena.

The mechanistic relationship of the inhibition of gap junctional intercellular communication (GJIC) to other toxicological phenomena was explored using a recently developed method that models the properties of a large population of molecules chosen to represent the 'universe of chemicals'. The analyses indicate that inhibition of GJIC is strongly linked to the carcinogenic process in rodents, to cellular but not systemic toxicity, to biological phenomena that may involve inflammatory processes and to development effects. The inhibition of GJIC appears not to be associated with genotoxic mechanisms. With respect to cancer causation, integration of the analyses suggests that inhibition of GJIC is involved in non-genotoxic cancer induction or in the non-genotoxic phases of the carcinogenic process (such as inflammation, cell toxicity, cell proliferation, inhibition of cell differentiation and apoptosis).

Animals↗