Cytolysins increase intracellular calcium and induce eicosanoids release by pheochromocytoma PC12 cell cultures. 1993

S A Raya, and V Trembovler, and E Shohami, and P Lazarovici
Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel.

Cytolysins are the most commonly occurring toxins among bacteria, plants, and animals. By distributing cell membrane, they impair ionic permeability, leading to cell death. In an attempt to investigate cytolysin action on catecholaminergic neurons, we have treated pheochromocytoma cell cultures with Streptolysin S, Staphylococcus aureus alpha and delta, Stoichatus, Parcelsin, and cobra direct lytic factor. To measure neurotoxicity, PC12 cultures were loaded with 51Cr and exposed for 1 hr at 37 degrees C to different concentrations of cytolysins. Cytotoxic dose-response curves have been generated resulting in CD50 (cytotoxic dose 50%) in the range of 1-50 micrograms toxin/culture. Using subcytotoxic concentrations of cytolysins (which are of clinical relevance), changes on intracellular calcium were measured by Fura-2 fluorescence technique. Addition of either Stoichatus toxin and tetanolysin or streptococcus and staphylococcus cytolysins to PC12 cells caused rapidly or gradually a progressive increase in [Ca2+]i, respectively. Under similar conditions, samples of PC12 culture medium were assayed for 3H-arachidonic acid released and by radioimmunoassay for the content of PGE2 (prostaglandin), TXB2 (stable metabolite of thromboxane), and 5-HETE (hydroxy acid lipoxygenase product). PLA2 was activated 4.5-6.0-fold and the levels of all three eicosanoids were increased by 2.5-9-fold (PGE2), 4-6-fold (TXB2), and over 100-fold (5-HETE) by Stoichatus and Parcelsin cytolysins. Upon treatment with Streptolysin S and staphylococcus delta toxins PLA2 (phospholipase A2) was slightly activated (1.5-fold) and the levels of PGE2 and TXB2 increased 1.3-2.0-fold and that of 5-HETE up to 30-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D009498 Neurotoxins Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. Alpha-Neurotoxin,Excitatory Neurotoxin,Excitotoxins,Myotoxin,Myotoxins,Neurotoxin,Alpha-Neurotoxins,Excitatory Neurotoxins,Excitotoxin,Alpha Neurotoxin,Alpha Neurotoxins,Neurotoxin, Excitatory,Neurotoxins, Excitatory
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003603 Cytotoxins Substances that are toxic to cells; they may be involved in immunity or may be contained in venoms. These are distinguished from CYTOSTATIC AGENTS in degree of effect. Some of them are used as CYTOTOXIC ANTIBIOTICS. The mechanism of action of many of these are as ALKYLATING AGENTS or MITOSIS MODULATORS. Cytolysins,Cytotoxic Agent,Cytotoxic Agents,Cytotoxin,Agent, Cytotoxic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015777 Eicosanoids A class of compounds named after and generally derived from C20 fatty acids (EICOSANOIC ACIDS) that includes PROSTAGLANDINS; LEUKOTRIENES; THROMBOXANES, and HYDROXYEICOSATETRAENOIC ACIDS. They have hormone-like effects mediated by specialized receptors (RECEPTORS, EICOSANOID). Eicosanoid,Icosanoid,Icosanoids
D016716 PC12 Cells A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation. Pheochromocytoma Cell Line,Cell Line, Pheochromocytoma,Cell Lines, Pheochromocytoma,PC12 Cell,Pheochromocytoma Cell Lines
D016718 Arachidonic Acid An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. (all-Z)-5,8,11,14-Eicosatetraenoic acid,Arachidonic Acid, (all-Z)-Isomer, 1-(14)C-Labeled,Arachidonic Acid, (all-Z)-isomer, 3H-Labeled,Arachidonic Acid, Ammonium Salt, (all-Z)-Isomer,Arachidonic Acid, Cerium Salt, (all-Z)-Isomer,Arachidonic Acid, Cesium Salt, (all-Z)-Isomer,Arachidonic Acid, Lithium Salt, (all-Z)-Isomer,Arachidonic Acid, Potassium Salt, (all-Z)-Isomer,Arachidonic Acid, Sodium Salt,Arachidonic Acid, Sodium Salt, (all-Z)-Isomer,Arachidonic Acid, Zinc Salt, (all-Z)-Isomer,Sodium Arachidonate,Vitamin F,Arachidonate, Sodium

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