Primary cultures of adult rat hepatocytes were treated in the presence or absence of extracellular calcium with ten different membrane-active toxins. In all cases more than half the cells were killed in 1 to 6 hours in the presence but not in the absence of extracellular calcium. An effect of calcium on the primary mechanism of membrane injury by any of the agents cannot be implicated. Viability, as determined by trypan blue exclusion correlated well with other indices of viability such as plating efficiency and the hydrolysis of fluorescein diacetate. It is concluded that the cells are killed by processes that involve at least two steps. In each type of injury, disruption of the integrity of the plasma membrane by widely differing mechanisms is followed by a common functional consequence involving extracellular calcium, and most likely representing an influx of calcium across the damaged plasma membrane and down a steep concentration gradient. This later step represents, or at least initiates, a final common pathway for the toxic death of these cells.

https://science.sciencemag.org/content/sci/206/4419/700.full.pdf

Calcium dependence of toxic cell death: a final common pathway

How do the polyene macrolide antibiotics affect the cellular membrane properties

Introduction Vitamin D is generally accepted as being essential for life in higher animals (278). It is one of the most important biological regulators of calcium and phosphorus (406) metabolism. Along with the two peptide hormones PTH and calcitonin, vitamin D is responsible for the minute-to-minute as well as the day-to-day establishment and maintenance of calcium homeostasis. The substance vitamin D, or cholecalciferol, was first identified through the nutritional studies of Sir Edward Mellanby (243), which identified rickets as a disease state resulting from a deficiency of vitamin D, as well as through the biochemical/chemical studies of McCollum and co-workers (242), who demonstrated that there was more than one fat-soluble vitamin. Together these studies established a deficiency state, namely rickets, which was attributable to the newly discovered, nutritionally important fat-soluble component, vitamin D. In retrospect, however, the most important discovery related to the appreciation by Huldschins...

The vitamin D endocrine system: steroid metabolism, hormone receptors, and biological response (calcium binding proteins).

New aspects of liposomes.

Iturins, a special class of pore-forming lipopeptides: biological and physicochemical properties.

Publisher Summary This chapter discusses the chemistry and structure of the class of polyene antibiotics. It also discusses the biology of the action of the polyenes in the affected organism and in both natural and artificial membrane systems. The polyene compounds amphotericin B and nystatin are the chief substances employed clinically. They have been employed in relieving dermatophytic infections and in treating monilial infections, particularly in obstetrical and gynecological cases. Additionally, the hypocholesterolemic activity of orally administered polyene antibiotics has been reported as has their possible use in treating prostatic hypertrophy. Elemental analyses of the polyene antibiotics indicate that they contain only carbon, hydrogen, oxygen, and, in some instances, nitrogen. The amino group present in some of the polyene antibiotics is associated with an amino sugar that is connected to the macrolide ring through a glycosidic bond. Polyene antibiotics are all characterized by a macrolide ring, which is a large ring of carbon atoms whose closure is affected by the formation of an internal ester or lactone. The presence of the lactone confers a highly characteristic peak on the infrared spectra of these compounds.

Polyene antibiotic - sterol interaction.

Studies on the mechanism of action of calciferol III. Vitamin D-mediated increase of intestinal brush border alkaline phosphatase activity

The production of 1,25-dihydroxycholecalciferol, the biologically active form of cholecalciferol (vitamin D3), was studied using homogenates or subcellular fractions incubated with 25-hydroxy-[26,27-3H]-cholecalciferol. It was found that only the kidney in the chick was capable of producing 1,25-dihydroxycholecalciferol. Also, kidney tissue obtained from the rat, dog and man produced, under in vitro conditions, a radioactive sterol which cochromatographed with standard 1,2 5-dihydroxycholecalciferol. The enzymatic activity was found to be located in the mitochondrial, but not the nuclear, microsomal or supernatant fractions of chick kidney. In the dog, the enzymatic production of 1,25-dihydroxycholecalciferol was found only in the kidney cortex and not in the medulla. It appears that in organisms utilizing cholecalciferol, the vitamin is converted to its active form by the kidney. Thus, the implication of the kidney in cholecalciferol metabolism may be of relevance to the pathogenesis of disorders of calc...

Studies on Calciferol Metabolism. VI. The Renal Production of the Biologically Active Form of Vitamin D, 1,25-Dihydroxycholecalciferol; Species, Tissue and Subcellular Distribution1

Vitamin D-mediated intestinal calcium transport: Effects of essential fatty acid deficiency and spin label studies of enterocyte membrane lipid fluidity☆

The polyene antibiotic, filipin, is known to interact with cholesterol present in aqueous solutions, artificial membranes and sterol-containing biological membranes. The stoichiometry of interaction between filipin and free or liposomal-bound cholesterol present in an aqueous system was determined by quantitating the ultraviolet spectral change of filipin which occurs in the presence of cholesterol. A preliminary analysis of the data obtained from aqueous dispersions of cholesterol + filipin alone suggested that the stoichiometry was 1:1. According to a more refined analysis of this same data by the SCATCHARD technique, there are 1.11±0.18 molecules of cholesterol associated with filipin in this system. Additionally it was found in a liposome solution consisting of lecithin : dicetylphosphate : [4-14C]-cholesterol that the maximum spectral change of filipin only occurred where a 1:1 ratio of filipin : sterol was present. Thus the likely stoichiometry of the filipin-cholesterol complex in both these systems is 1:1.A procedure is described wherein the sterol-mediated spectral-change of filipin can be utilized as the basis of a sensitive assay for quantitating the amounts of sterol in membrane fractions.

Anna M. Spielvogel

Papers

Polyene antibiotic - sterol interaction.

Studies on the mechanism of action of calciferol III. Vitamin D-mediated increase of intestinal brush border alkaline phosphatase activity

Studies on Calciferol Metabolism. VI. The Renal Production of the Biologically Active Form of Vitamin D, 1,25-Dihydroxycholecalciferol; Species, Tissue and Subcellular Distribution1

Vitamin D-mediated intestinal calcium transport: Effects of essential fatty acid deficiency and spin label studies of enterocyte membrane lipid fluidity☆

Stoichiometry of interaction of the polyene antibiotic, filipin, with free and liposomal-bound cholesterol.