Study on the Acute Eye Toxicity of PP1 Liposomes / 中国药师

Objective:To observe the acute toxic side effects of liposome PP 1 topically applied in eyes .Methods:PP1 liposomes (10, 60, 400 μmol· L-1 ) were used in one eye of SD rats , 4 times daily.The changes of conjunctiva , cornea and iris were observed under the slit-lamp biomicroscope , for three consecutive days , and evaluated by the stimulus score sheet of anterior segment .One week after the treatment , the corneas , irises and lenses were isolated , and their changes were observed under the light microscope .The ul-trastructural changes of corneal epithelial cells and endothelial cells were observed under the electron microscope .Results:There was a little of conjunctival secretion in one rat in the first day after the treatment with 400 μmol· L-1 PP1 liposomes, and the other rats were not irritant reaction .The corneal fluorescein staining of all rats were negative .The structures of cornea , iris, lens tissue were normal after given different concentrations of PP1 liposomes.Conclusion:PP1 liposomes at Low, medium and high concentrations show no a-cute eye toxicity in SD rats .

The evolutionary strata of DARPP-32 tail implicates hierarchical functional expansion in higher vertebrates.

DARPP-32 (dopamine and adenosine 3′,5′-monophosphate-regulated phosphoprotein of 32 kDa), which belongs to PPP1R1 gene family, is known to act as an important integrator in dopamine-mediated neurotransmission via the inhibition of protein phosphatase-1 (PP1). Besides its neuronal roles, this protein also behaves as a key player in pathological and pharmacological aspects. Use of bioinformatics and phylogenetics approaches to further characterize the molecular features of DARPP-32 can guide future works. Predicted phosphorylation sites on DARPP-32 show conservation across vertebrates. Phylogenetics analysis indicates evolutionary strata of phosphorylation site acquisition at the C-terminus, suggesting functional expansion of DARPP-32, where more diverse signalling cues may involve in regulating DARPP-32 in inhibiting PP1 activity. Moreover, both phylogenetics and synteny analyses suggest de novo origination of PPP1R1 gene family via chromosomal rearrangement and exonization.

Effects of maternal deprivation on hippocampal PP1Cγ gene expression and neurobehavior of rats / 中华行为医学与脑科学杂志

Objective To investigate the effect of maternal deprivation (MD) on neurobehavior and PP1Cγgene expression in hippocampus. Methods Male pups were randomly divided into MD group(thirty-five)and control group(twenty-four). From PND 1 to PND 21 ,pups in the MD groups underwent daily maternal deprivation for 3 h ( Postnatal day). Neurobehavior was observed to investigate neurodevelopment, Morris water maze was used to measure spatial learning and memory,and Real-Time quantitative PCR was employed to analyze PP1Cγ gene expression. Results Several significant deficiencies were observed in bodyweight and grasping reflex while a great enhancement in hot-plate test in rat pups suffering from MD( (26.23 ± 2.81 )g vs. (30. 38 ± 3.85 )g;( 19.37 ± 11.89) s vs. (22.39 ± 17.62 ) s; (4.36 ± 1.76 ) s vs. ( 5.26 ± 2.55 ) s; P ＜ 0. 05 ), but deficiencies in neurological reflexes were subtle ( ( 0.83 ±- 0.30 ) s vs. ( 0. 83 ± 0. 34 ) s; ( 3.68 ± 1.63 ) s vs. ( 5.61 ± 3. 01 ) s;( 3.00 ± 0.00 ) vs. ( 3.00 ± 0. 00); P ＞ 0. 05 ). MD had a subtle influence on spatial learning and memory (P ＞0.05). Meanwhile,MD could lead to PP1Cγ expression down-regulation on PND 22 ( (2.19 ±0.62) vs. (3.52 ±0.86), P＜0. 05)which was in line with early neurobehavior results. No difference was found compared with MD group and control group on PND60 ( ( 1.73 ± 0. 78 ) vs. ( 1.33 ± 0. 34); P ＞ 0.05 ). However, there was the up-regulation of PP1Cγexpression on PND 90 ( (2.85 ± 0. 34) vs. ( 1.34 ± 0.93 ); P ＜ 0.05 ). Conclusion MD alters early neurobehavior and hippocampal PP1Cγgene expression in the Wistar rats,but has a subtle effect on learning and memory. At the same time,MD can make PP1Cγexpression in the hippocampus varying with the age.

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.

Identification the rare p phenotype in serological and molecular biological methods / 中国输血杂志

Objective To identify the p phenotype. Method P blood group system was identified using p phenotype cells,anti PP 1 P k antiserum,and direct DNA sequencing.Result and Conclusion Proband was typed as p, with rare anti PP 1 P k in the serum,family study suggested that inheritance was autosomal recessive.