ADP-ribosylation of regulatory proteins is an important pathological mechanism by which various bacterial toxins affect eukaryotic cell functions. While diphtheria toxin catalyses the ADP-ribosylation of elongation factor 2, which results in inhibition of protein synthesis, cholera toxin and pertussis toxin ADP-ribosylate Ns and Ni, respectively, the GTP-binding regulatory components of the adenylate cyclase system, thereby modulating the bidirectional hormonal regulation of the adenylate cyclase. Botulinum C2 toxin is another toxin which has been reported to possess ADP-ribosyltransferase activity. This extremely toxic agent is produced by certain strains of Clostridium botulinum and induces hypotension, an increase in intestinal secretion, vascular permeability and haemorrhaging in the lungs. In contrast to botulinum neurotoxins, the botulinum C2 toxin apparently lacks any neurotoxic effects. Here we report that botulinum C2 toxin ADP-ribosylates a protein of relative molecular mass 43,000 (43K) in intact cells and in cell-free preparations. We present evidence that the 43K protein substrate is actin, which is apparently mono-ADP-ribosylated by the toxin. Botulinum C2 toxin also ADP-ribosylated purified liver G-actin, whereas liver F-actin was only poorly ADP-ribosylated and skeletal muscle actin was not ADP-ribosylated in either its G form or its F form. ADP-ribosylation of liver G-actin by botulinum C2 toxin resulted in a drastic reduction in viscosity of actin polymerized in vitro.

Actins↗

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Advantages and pitfalls of particulate brain and membranes in neurotoxicological studies.

Specific neurotoxins, for instance from animal and bacterial origin, are important tools for the neurobiologist. In contrast, the neurotoxicologist deals mainly with nonspecific agents acting on many central and peripheral functions simultaneously. Specific actions are well reproducible with subcellular systems, whereas the validity of data obtained on isolated systems with nonspecific agents is to be doubted until support is found in vivo. Use of isolated systems raises the precision, reproducibility and transparency of a biological event of toxicological interest, but at the same time obscures its relevance and its predictive value.

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PubMedDate not supplied

A technique for investigating the antigenicity of cultured rheumatoid synovial cells.

Antisera to rheumatoid and nonrheumatoid synovial cells were prepared by: intraarticular injection of rabbits with these cells, subsequent synovectomy, and autologous immunization of each animal with the cultured rabbit synovial cells, or homogenized whole rabbit synovial membrane. Resultant antisera were studied by immunofluorescence and 51chromium cytotoxicity tests against other cultured rheumatoid and nonrheumatoid cells. Activity of positive sera could be removed by absorption with nonrheumatoid cells, except for one antiserum which appeared to produce immunofluorescent staining specific for rheumatoid cells.

Animals↗