Phytotoxicity associated to microcystins: a review / Fitotocixidade associada às microcistinas: uma revisão

Microcystins (MC) are the most studied toxins of cyanobacteria since they are widely distributed and account for several cases of human and animal poisoning, being potent inhibitors of the serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A). The phosphatases PP1 and PP2A are also present in plants, which may also suffer adverse effects due to the inhibition of these enzymes. In aquatic plants, biomass reduction is usually observed after absorption of cyanotoxins, which can bioaccumulate in its tissues. In terrestrial plants, the effects caused by microcystins vary from inhibition to stimulation as the individuals develop from seedling to adult, and include reduction of protein phosphatases 1 and 2A, oxidative stress, decreased photosynthetic activity and even cell apoptosis, as well as bioaccumulation in plant tissues. Thus, the irrigation of crop plants by water contaminated with microcystins is not only an economic problem but becomes a public health issue because of the possibility of food contamination, and this route of exposure requires careful monitoring by the responsible authorities.

Microcistinas (MC) são as toxinas de cianobactérias mais estudadas, uma vez que são amplamente distribuídas e responsáveis por vários casos de intoxicação humana e animal. São potentes inibidoras das proteínas fosfatases serina/treonina 1 (PP1) e 2A (PP2A). As fosfatases PP1 e PP2A também estão presentes em plantas, as quais podem sofrer efeitos adversos devido à inibição dessas enzimas. Em plantas aquáticas, a redução da biomassa é geralmente observada após absorção de cianotoxinas que podem bioacumular em seus tecidos. Em plantas terrestres, os efeitos causados pelas microcistinas variam de inibição ao estímulo, como no desenvolvimento de plântulas ao estádio adulto, e incluem a redução de proteínas fosfatases 1 e 2A, estresse oxidativo, diminuição da atividade fotossintética e até mesmo apoptose celular, bem como a bioacumulação em tecidos de plantas. Assim, a irrigação de plantas cultivadas com água contaminada com microcistina não é apenas um problema econômico, mas torna-se um problema de saúde pública, devido à possibilidade de contaminação dos alimento, sendo uma via de exposição que requer um monitoramento cuidadoso por parte das autoridades responsáveis.

PPM1B and P-IKKβ expression levels correlated inversely with rat gastrocnemius atrophy after denervation

Activated inhibitor of nuclear factor-κB kinase β (IKKβ) is necessary and sufficient for denervated skeletal muscle atrophy. Although several studies have shown that Mg2+/Mn2+-dependent protein phosphatase 1B (PPM1B) inactivated IKKβ, few studies have investigated the role of PPM1B in denervated skeletal muscle. In this study, we aim to explore the expression and significance of PPM1B and phosphorylated IKKβ (P-IKKβ) during atrophy of the denervated gastrocnemius. Thirty young adult female Wistar rats were subjected to right sciatic nerve transection and were sacrificed at 0 (control), 2, 7, 14, and 28 days after denervation surgery. The gastrocnemius was removed from both the denervated and the contralateral limb. The muscle wet weight ratio was calculated as the ratio of the wet weight of the denervated gastrocnemius to that of the contralateral gastrocnemius. RT-PCR and Western blot analysis showed that mRNA and protein levels of PPM1B were significantly lower than those of the control group at different times after the initiation of denervation, while P-IKKβ showed the opposite trends. PPM1B protein expression persistently decreased while P-IKKβ expression persistently increased for 28 days after denervation. PPM1B expression correlated negatively with P-IKKβ expression by the Spearman test, whereas decreasing PPM1B expression correlated positively with the muscle wet weight ratio. The expression levels of PPM1B and P-IKKβ were closely associated with atrophy in skeletal denervated muscle. These results suggest that PPM1B and P-IKKβ could be markers in skeletal muscle atrophy.

Effects of intrahippocampal administration of the phosphatase inhibitor okadaic acid: dual effects on memory formation / Efeitos da administração intra-hipocampal do inibidor de fosfatases ácido okadaico: efeito duplo sobre a formação de memória

Protein phosphorylation mediated by serine-threonine kinases in the hippocampus is crucial to the synaptic modifications believed to underlie memory formation. The role of phosphatases has been the focus of comparatively little study. Objectives: Here we evaluate the contribution of the serine-threonine protein phosphatases 1 and 2A (PP1, PP2A) on memory consolidation. Methods: We used immediate post-training bilateral hippocampal infusions of okadaic acid (OA, 0.01 and 10 pmol/side), a potent inhibitor of PP1 and PP2A, and measured short- [3 h] and long-term memory [24 h] (STM, LTM) of step-down inhibitory avoidance. Results: At the lower dose, OA inhibited both STM and LTM whereas at the higher dose it instead enhanced LTM. Pre-test infusion of these two doses of OA had no effect on retrieval. Conclusions: These two doses of OA are known to selectively inhibit PP1 and PP2A respectively. These findings point to the importance of these enzymes in memory formation and also suggest a deleterious influence of endogenous hippocampal PP2A on LTM formation.

A fosforilação de proteínas mediada por serina-treonina quinases no hipocampo é crucial para as modificações sinápticas que se acredita sejam necessárias para a formação de memórias. O papel das fosfatases tem sido comparativamente pouco estudado. Objetivos: Aqui avaliamos a contribuição das fosfatases serina-treonina 1 e 2 (PP1, PP2A) sobre a consolidação da memória. Métodos: Usamos infusões imediatamente após o treino de ácido okadaico (OA, 0.01 e 10 pmol/lado), um potente inibidor de PP1 e medimos memória de curta [3 h] e longa duração [24 h] (STM, LTM) de esquiva inibitória de evitar descer de uma plataforma. Resultados: Na dose menor, OA inibiu tanto STM como LTM. Na dose maior, produziu, em vez disso, uma melhora da LTM. A infusão pré-teste de qualquer uma das duas doses de OA não teve efeito sobre a evocação. Conclusões: Estas duas doses de OA são conhecidas por inibir seletivamente PP1 a PP2 respectivamente. Estes resultados apontam à importância das duas enzimas na formação de memória e sugerem, adicionalmente, uma influência deletérea da PP2A endógena sobre a formação de LTM.