Protein synthesis inhibition cylindrospermopsins

Froscio SM, Humpage AR, Burcham PC, Falconer IR (2003) Cylindrospermopsin-induced protein synthesis inhibition and its dissociation from acute toxicity in mouse hepatocytes. Environ Toxicol 18 243-251... 

Cylindrospermopsin resulted in a hepatotoxic alkaloid that is capable of inhibiting protein synthesis, and it appears to have a progressive effect on several other vital organs snch as the kidney in addition to the liver (Terao 1994 Falconer 1999). Cylindrospermopsin was shown to be a potent inhibitor of protein synthesis. The same stndies described the liver as the main target of this phyco-toxin, with four consecutive phases of the pathological changes in the liver protein synthesis inhibition, membrane proliferation, fat droplet accumulation, and cell death. 

The main target tissue of purified cylindrospermopsin toxicosis is the liver, but several other tissues are also affected, including the kidneys, thymus, and heart (Terao et al., 1994). Cylindrospermopsin is a potent inhibitor of protein synthesis, but the exact mechanism of action has not been elucidated. Four sequential phases of hepatocyte damage were identified by time-series analysis, including protein synthesis inhibition, membrane proliferation, lipid infiltration, and necrosis. Cylindrospermopsin has been shown to cause DNA... 

Not surprisingly, the toxin s liver toxicity is reflected by the ability of micromolar concentrations of cylindrospermopsin to kill in vitro liver cells such as rat hepatocytes and the human hepatoblastoma cell line HEP-G2. Cylindrospermopsin is known to potently inhibit cellular protein synthesis that can be measured in vitro using rabbit reticulocyte lysate. 

Hepatotoxins include microcystins, which are cyclic heptapeptides (Fig. 5.1a) and cylindrospermopsin, a sulfated guanidinium alkaloid (Fig. 5. lb). Microcystins bind to certain protein phosphatases responsible for regulating the distribution of cytoskeletal proteins (Zurawell et al. 2005 Leflaive and Ten-Hage 2007). Hepatocytes exposed to microcystins eventually undergo cellular deformation, resulting in intra-hepatic bleeding and, ultimately, death (Carmichael 2001 Batista et al. 2003). In contrast, cylindrospermopsin appears to have a different mode of activity, possibly involving inhibition of protein or nucleotide synthesis (Codd et al. 1999 Froscio et al. 2003 Reisner et al. 2004). Nevertheless, microcystins are the most common cyanotoxins isolated from cyanobacterial blooms (Sivonen and Jones 1999). 

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