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Toxicity of ricin and volkensin, two ribosome‐inactivating proteins, to microglia, astrocyte, and neuron cultures
Author(s) -
Sparapani Mauro,
Buonamici Laura,
Ciani Elisabetta,
Battelli Maria Giulia,
Ceccarelli Gianluca,
Stirpe Fiorenzo,
Contestabile Antonio
Publication year - 1997
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199707)20:3<203::aid-glia4>3.0.co;2-8
Subject(s) - ricin , microglia , biology , astrocyte , in vivo , toxicity , ribosome inactivating protein , protein biosynthesis , neuroglia , in vitro , biochemistry , microbiology and biotechnology , toxin , ribosome , immunology , chemistry , rna , central nervous system , inflammation , neuroscience , organic chemistry , gene
Ricin and volkensin, two potent toxins belonging to the family of ribosome‐ inactivating proteins (RIPs), have been largely exploited in recent years in in vivo experiments of neuronal degeneration consequent to suicide transport or immunolesioning. We have determined both the toxicity of, and the inhibition of, protein synthesis by ricin and volkensin in in vitro cultures enriched in microglial cells, astrocytes, or neurons. In microglial cultures, 50% of toxicity (estimated by LDH released from dead cells) after 24 h exposure to RIPs was obtained with volkensin at 2.2×10 −12 M concentration and 50% of protein synthesis inhibition at 2×10 −14 M concentration. Both values were higher by about one order of magnitude in astrocyte‐enriched cultures. Toxicity of, and inhibition of, protein synthesis by, ricin were lower for both cell types by about 1 order of magnitude as compared to volkensin. Cerebellar granule neurons in culture survived remarkably well to 24 h exposure to ricin or volkensin, although their protein synthesis was effectively inhibited by the two toxins with a potency similar to that found for astrocytes. These results demonstrate that glial cells, in particular microglia, are very sensitive to RIPs toxicity and should, therefore, be a primary target of these toxins when injected in vivo. Thus, the damage observed after in vivo experiments could be partly related to diffusion of toxic substances from early‐affected glial cells. GLIA 20:203‐209, 1997. © 1997 Wiley‐Liss, Inc.