Actin cytoskeleton of rabbit intestinal cells is a target for potent marine phycotoxins

Abstract

Biotoxins produced by harmful marine microalgae (phycotoxins) can be accumulated into seafood, representing a great risk for public health. Some of these phycotoxins are responsible for a variety of gastrointestinal disturbances; however, the relationship between their mechanism of action and toxicity in intestinal cells is still unknown. The actin cytoskeleton is an important and highly complicated structure in intestinal cells, and on that basis our aim has been to investigate the effect of representative phycotoxins on the enterocyte cytoskeleton. We have quantified for the first time the loss of enterocyte microfilament network induced by each toxin and recorded fluorescence images using a laser-scanning cytometer and confocal microscopy. Our data show that pectenotoxin-6, maitotoxin, palytoxin and ostreocin-D cause a significant reduction in the actin cytoskeleton. In addition, we found that the potency of maitotoxin, palytoxin and ostreocin-D to damage filamentous actin is related to Ca 2+ influx in enterocytes. Those results identify the cytoskeleton as an early target for the toxic effect of those toxins.

Accumulation, transformation and breakdown of DSP toxins from the toxic dinoflagellate Dinophysis acuta in blue mussels, Mytilus edulis

“…Pectenotoxins disrupt actin in the cytoskeleton, and may cause cell cycle arrest and cell death (Spector et al, 1999;Ares et al, 2005;Anonymous, 2009). Thus, accumulation of both toxin groups is undesirable at best.…”

The methyl ester of okadaic acid is more potent than okadaic acid in disrupting the actin cytoskeleton and metabolism of primary cultured hepatocytes

“…Hepatic-enteric cell models are particularly useful in studying the effect of hepatotoxins and DSP-related toxins (Louzao et al, 2003;Ares et al, 2005;. At this cellular level, primary cultured cells isolated from rodents' liver are common in vitro models; also immortalized hepatocytes offer a renewable source of hepatocytes.…”

“…Studying the effect of this toxin on hepatic cells is thus fundamental to a better understanding of the pharmacokinetics and pharmacodynamics of MeOk (Gomez-Lechon et al, 2004). In addition, hepatic cells have some characteristics very appropriate to our study, such as glucose uptake and the marked actin cytoskeletal structure (Oda et al, 2008).Hepatic-enteric cell models are particularly useful in studying the effect of hepatotoxins and DSP-related toxins (Louzao et al, 2003;Ares et al, 2005;. At this cellular level, primary cultured cells isolated from rodents' liver are common in vitro models; also immortalized hepatocytes offer a renewable source of hepatocytes.…”

“…However, the cells did not show the characteristic F-actin punctuated distribution, consequence of the treatment with other natural compounds that disorganize the actin cytoskeleton, for instance, pectenotoxins. These toxins disrupt the actin cytoskeleton of many kinds of cells, depolymerizing F-actin and preventing its polymerization (Ares et al, 2005;Ares et al, 2007;Espina and Rubiolo, 2008;. It is not clear yet if the extensive reorganization of the actin cytoskeleton induced by OA is a direct consequence of its activity or if it is an indirect consequence of the normal apoptotic process.…”

Disruption of blastomeric F-actin: a potential early biomarker of developmental toxicity in zebrafish

“…In culture, cancerous and undifferentiated mammalian cells have weaker actin cytoskeletons than normal cells [38,39]. Cellular F-actin and monomeric G-actin (depolymerized F-actin) levels have been used as biomarkers of bladder cancer risk, breast cancer, prostate adenocarcinoma and cholestasis [37,[40][41][42], hepatotoxicity caused by pectenotoxins [43][44][45][46], and nanoparticle-induced toxicity [47]. Moreover, actin remodeling has been contemplated as a potential target for cancer drug development [48].…”