Marine algal blooms, natural phenomena produced by the
overgrowth of microscopic marine algae, have become a public
health concern because of their increasing frequency and
severity. About 300 phytoplanktonic species are known to have
the ability to cause these blooms, and one-fourth of them are
able to produce toxins, also called phycotoxins. Shellfish, mainly
bivalve mollusks, and fish may accumulate these phycotoxins by
direct filtration of the producer algal cells or by feeding on
contaminated organisms. Human intoxications caused by phycotoxins occur worldwide through consumption of marine
fishery products containing bioaccumulated toxins.
According to their toxic effects and chemical properties,
phycotoxins are classified into different categories. Diarrheic
shellfish poisoning (DSP) toxins are one of the most relevant
groups of the phytoplanktonic toxins because its presence
produces not only severe economic losses, but also health effects
in human consumers. The first registered DSP episode after
shellfish consumption occurred in 1961 in The Netherlands.
However, no relationship with the phycotoxins was established
at that time. It was in 1976 when the association between the
frequent occurrence of gastroenteritis and the ingestion of phycotoxin-contaminated shellfish was proved the first time. Since
then, a large number of DSP episodes have been documented
worldwide. However, this number is believed to be much higher
because these episodes are not often well documented for the
reason that the acute symptoms are sometimes light and
intoxicated people do not always require medical assistance.
Okadaic acid (OA) and its analogs, the dinophysistoxins
(DTX), are lipophilic marine toxins produced by several phytoplanktonic species and responsible for DSP in humans.
OA, the main representative toxin of this group, was first isolated in 1981 from the black sponge Halichondria okadai as well
as from H. melanodocia. It is usually accumulated by several
marine organisms, mainly bivalve mollusks, by eating phytoplankton containing OA. This toxin is highly distributed all over the world, but is especially abundant in Japan in Europe.
OA exposure can represent a severe threat to human health
beyond its DSP effects, because it was demonstrated to be
a specific inhibitor of several types of serine/threonine protein
phosphatases and a tumor promoter in animal carcinogenesis
experiments.
OA is a natural marine toxin produced by different phytoplanktonic species mainly from the dynoflagellates group. It
may pass through the food chain to humans who ingest OAcontaminated organisms. Thus, it does not have any commercial applications in medicine, food, construction, or similar
industries. However, because of its well-known ability to
selectively inhibit several types of serine/threonine protein
phosphatases, it is often used in research as a useful tool for
studying cellular processes regulated by reversible phosphorylation of proteins, including control of glycogen metabolism,
coordination of the cell cycle and gene expression, and maintenance of cytoskeletal structure.
Furthermore, it was reported that other marine toxins,
different from OA, can also act as specific protein phosphatase
(mainly PP1 and PP2A) inhibitors. They are called OA class
tumor promoters and were proved to be able to cause skin,
stomach, and liver tumors in animals. This has led some authors
to suggest a new concept of tumor promotion: the okadaic acid
pathway. In this regard, studies with OA, as well as with other
OA class tumor promoters, could deepen the knowledge of the
mechanisms of cancer development in humans.
Biochemical tool as tumor promoter and probe of cellular regulation.
Okadaic acid is a widely distributed marine toxin produced by several phytoplanktonic species and responsible for diarrheic shellfish poisoning in humans. At the molecular level, Okadaic acid is a pot
ent and specific inhibitor of various types of serine/threonine protein phosphatases. Due to this enzymatic inhibition, Okadaic acid was reported to induce numerous alterations in relevant cellular ph
ysiological processes, including metabolic pathways such as glucose uptake, lipolysis and glycolysis, heme metabolism and glycogen and protein synthesis.
ChEBI: Okadaic acid is a polycyclic ether that is produced by several species of dinoflagellates, and is known to accumulate in both marine sponges and shellfish. A polyketide, polyether derivative of a C38 fatty acid, it is one of the primary causes of diarrhetic shellfish poisoning (DSP). It is a potent inhibitor of specific protein phosphatases and is known to have a variety of negative effects on cells. It has a role as a marine metabolite, an EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor and a calcium ionophore.
Okadaic acid is a polyether fatty acid. It is a marine toxin produced by the genera of Prorocentrum?and?Dinophysis.
Potent inhibitor of protein phosphatase 1 (IC 50 = 3 nM) and protein phosphatase 2A (IC 50 = 0.2-1 nM). Displays > 100,000,000-fold selectivity over PP2B and PP2C. Tumor promotor. Shown to activate atypical protein kinase C in adipocytes.
Dinoflagellate toxin and an ionophore-like polyether derivative of a 38 carbon, fatty acid. Readily enters cells. Inhibitor of type 1 and type 2A protein phosphatases. Does not inhibit tyrosine phosphatases, alkaline phosphatases or acid phosphatase. Known tumor promotor. Used to study various cellular processes including cell cycle, apoptosis, nitric oxide metabolism and calcium signaling.
A poison by intraperitoneal route.Questionable carcinogen. Mutation data reported. Whenheated to decomposition it emits acrid smoke andirritating vapors
As the main representative DSP toxin, OA ingestion leads to the
onset of acute gastrointestinal symptoms typical of this intoxication (e.g., diarrhea, nausea, vomiting, abdominal pain). It
was suggested that diarrhea in humans is caused by hyperphosphorylation of ion channels in intestinal cells impairing
the water balance, or by increased phosphorylation of cytoskeletal or junctional elements that regulate solute permeability, resulting in passive loss of fluids. It was also suggested
that OA causes long-lasting contraction of smooth muscle from
human and animal arteries.
At the molecular level, OA is a potent tumor promoter
and a recognized inhibitor of serine/threonine protein
phosphatases type 1 (PP1) and 2A (PP2A); PP2A is about
200 times more strongly inhibited than PP1. However,
nowadays OA is also known to inhibit PP4, and less effi-
ciently, PP5 and PP2B. This phosphatase activity inhibition
causes a dramatic increase in the phosphorylation levels of
numerous proteins that ultimately results in alterations of
relevant cell processes.
Mostly because of this ability, OA was shown to induce
severe cytotoxic effects that include cell cycle alterations,
morphological changes, apoptosis, viability decreases, and
cytoskeleton disruptions on different cell systems. Besides,
genotoxicity after OA exposure was also reported (see Genotoxicity section), and it was also demonstrated to alter geneexpression patterns in OA-exposed cells. The existence of
OA-binding proteins other than phosphatases has been
demonstrated in several marine organisms but not in
humans.
Although this toxin is not classified as a neurotoxin, it was
shown to induce some neurotoxic effects both in vitro and
in vivo. In vitro, OA induces apoptosis in a variety of human
and animal neurons, generates redistribution of neuronal
proteins, forces differentiated neuronal cells into the mitotic
cycle, induces disintegration of neuritis, and generates
changes in microtubule-associated proteins concomitant
with early changes in neuronal cytoskeleton. In vivo, OA
exposure was observed to produce inactivity and weakness in
mice as well as hyperexcitation, spatial memory deficit, and
neurodegeneration.
