The Administration of Cadmium for 2, 3 and 4 Months Causes a Loss of Recognition Memory,Promotes Neuronal Hypotrophy and Apoptosis in the Hippocampus of Rats

Cadmium (Cd) is a toxic metal and classified as a carcinogen whose exposure could affect the function of the central nervous system. There are studies that suggest that Cd promotes neurodegeneration in different regions of the brain, particularly in the hippocampus. It is proposed that its mechanism of toxicity maybe by an oxidative stress pathway, which modifies neuronal morphology and causes the death of neurons and consequently affecting cognitive tasks. However, this mechanism is not yet clear. The aim of the present work was to study the effect of Cd administration on recognition memory for 2, 3 and 4 months, neuronal morphology and immunoreactivity for caspase-3 and 9 in rat hippocampi. The results show that the administration of Cd decreased recognition memory. Likewise, it caused the dendritic morphology of the CA1, CA3 and dentate gyrus regions of the hippocampus to decrease with respect to the time of administration of this heavy metal. In addition, we observed a reduction in the density of dendritic spines as well as an increase in the immunoreactivity of caspase-3 and 9 in the same hippocampal regions of the animals treated with Cd. These results suggest that Cd affects the structure and function of the neurons of the hippocampus, which contribute to the deterioration of recognition memory. Our results suggest that the exposure to Cd represents a critical health problem, which if not addressed quickly, could cause much more serious problems in the quality of life of the human population, as well as in the environment in which they develop.

     

A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine phosphatase

Protein tyrosine phosphatase PTP-SL retains mitogen-activated protein (MAP) kinases in the cytoplasm in an inactive form by association through a kinase interaction motif (KIM) and tyrosine dephosphorylation. The related tyrosine phosphatases PTP-SL and STEP were phosphorylated by the cAMP-dependent protein kinase A (PKA). The PKA phosphorylation site on PTP-SL was identified as the Ser(231) residue, located within the KIM. Upon phosphorylation of Ser(231), PTP-SL binding and tyrosine dephosphorylation of the MAP kinases extracellular signal-regulated kinase (ERK)1/2 and p38alpha were impaired. Furthermore, treatment of COS-7 cells with PKA activators, or overexpression of the Calpha catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38alpha by wild-type PTP-SL, but not by a PTP-SL S231A mutant. These findings support the existence of a novel mechanism by which PKA may regulate the activation and translocation to the nucleus of MAP kinases.     

Biochemical and physiological changes produced by Azotobacter chroococcum (INIFAT5 strain) on pineapple in vitro-plantlets during acclimatization

This study highlights some of the effects of the application of Azotobacter chroococcum (INIFAT5 strain) on in vitro-pineapple plantlets during acclimatization. The bacteria were sprayed immediately after transplanting to the ex vitro environment; the plants were then sprayed every 4 week. Subsequently (4 months) the evaluated variables included plantlet fresh and dry weights, leaf and root lengths, and composition of minerals, amino-acids, carbohydrates and proteins. Photosynthesis indicators were also evaluated. Significant effects of the application of Azotobacter over pineapple plantlets during acclimatization were observed in the mineral, amino-acid, carbohydrate and protein levels, as well as, in the photosynthesis indicators. Contrastingly, plant growth parameters showed modest increases caused by the bacteria, although they were statistically significant. Looking into specific minerals, the following significant effects of Azotobacter should be highlighted: increased levels of nitrogen, phosphorous, potassium, magnesium, copper and zinc. Moreover, contents of all amino-acids recorded showed significant increases in their levels in sprayed plantlets. Carbohydrates were also increased in leaves of plantlets bio-fertilized with the bacteria, mainly sucrose and fructose. Chlorophyll b levels were also significantly increased by Azotobacter. The biofertilizer did not modify levels of calcium, iron or manganese.     

Seed dynamics of an endemic palm in a Northwestern Mexican tropical dry forest: implications for population spatial structure

Seed dynamics are an important part of the life history of plants and may have strong implications on abundance and spatial distribution of populations. In this study, we explored how seed dynamics (removal, predation, germination) interact with micro-environmental conditions to affect the spatial structure of populations of Brahea aculeata (Arecaceae) in a tropical dry forest. B. aculeata is distributed throughout arroyo basins and attains its highest densities near to arroyos/rivers. We hypothesized that: (i) seed removal, predation and germination vary across topographic positions resulting in greater palm abundances adjacent to arroyos and (ii) seed removers/predators respond to both a seed density-dependent effect and a microclimate effect. To test this, in six arroyos basins, seeds were sown across three topographic positions (stream, mid and top of basins) with two seed abundances (1 and 10), protected and non-protected from potential predators. Predation, removal and germination were then followed. After 107 days, 100 % of the exposed seeds were removed/predated and none germinated. For seed removal, we found differences among topographic positions and seed densities with higher removal (up to 80 %) and lower predation rates for grouped seeds. Germination was only observed for protected seeds with higher germination rates in single (17 % ± 9) than in grouped seeds (4 % ± 1). The highest germination and establishment rates were adjacent to the streams; areas which had the lowest light intensity (mean ± SE = 883 ± 160 lm/ft²) and temperatures (mean ± SE = 20.1 ± 0.6 °C), and highest humidity (mean ± SE = 50.8 ± 1.8 %), especially during the rainy season. Differential seedling establishment rates across the landscape due to spatial patterns of seed predation/removal as well as micro-environmental variables appear to have implications for shaping the spatial structure of B. aculeata population at Sierra de Álamos, Mexico.     

A novel phosphatase family, structurally related to dual-specificity phosphatases, that displays unique amino acid sequence and substrate specificity

Members of the superfamily of protein tyrosine phosphatases (PTPs) share the presence of an evolutionarily conserved PTP catalytic domain. Among them, the dual-specificity phosphatases (DSPs) constitute a diverse group of enzymes in terms of substrate specificity, including nonprotein substrates. In recent years, an increasing number of novel DSPs, whose functions and biological substrates are not well defined, have been discovered in a variety of organisms. In this study, we define the structural and functional properties of evolutionarily related atypical DSPs from different phyla. Sets of conserved motifs were defined that (i) uniquely segregated mammalian atypical DSPs from closely related enzymes and (ii) exclusively characterised a novel family of atypical DSPs present in plants, fungi, and kinetoplastids [plant and fungi atypical (PFA)-DSPs]; despite having different sequence “fingerprints,” the PTP tertiary structure of PFA-DSPs is conserved. Analysis of the catalytic properties of PFA-DSPs suggests the existence of a unique substrate specificity for these enzymes. Our findings predict characteristic functional motifs for the diverse members of the DSP families of PTPs and provide insights into the functional properties of DSPs of unknown function.     

Phosphorylation of the kinase interaction motif in mitogen-activated protein (MAP) kinase phosphatase-4 mediates cross-talk between protein kinase A and MAP kinase signaling pathways

MAP kinase phosphatase 4 (DUSP9/MKP-4) plays an essential role during placental development and is one of a subfamily of three closely related cytoplasmic dual-specificity MAPK phosphatases, which includes the ERK-specific enzymes DUSP6/MKP-3 and DUSP7/MKP-X. However, unlike DUSP6/MKP-3, DUSP9/MKP-4 also inactivates the p38α MAP kinase both in vitro and in vivo. Here we demonstrate that inactivation of both ERK1/2 and p38α by DUSP9/MKP-4 is mediated by a conserved arginine-rich kinase interaction motif located within the amino-terminal non-catalytic domain of the protein. Furthermore, DUSP9/MKP-4 is unique among these cytoplasmic MKPs in containing a conserved PKA consensus phosphorylation site (55)RRXSer-58 immediately adjacent to the kinase interaction motif. DUSP9/MKP-4 is phosphorylated on Ser-58 by PKA in vitro, and phosphorylation abrogates the binding of DUSP9/MKP-4 to both ERK2 and p38α MAP kinases. In addition, although mutation of Ser-58 to either alanine or glutamic acid does not affect the intrinsic catalytic activity of DUSP9/MKP-4, phospho-mimetic (Ser-58 to Glu) substitution inhibits both the interaction of DUSP9/MKP-4 with ERK2 and p38α in vivo and its ability to dephosphorylate and inactivate these MAP kinases. Finally, the use of a phospho-specific antibody demonstrates that endogenous DUSP9/MKP-4 is phosphorylated on Ser-58 in response to the PKA agonist forskolin and is also modified in placental tissue. We conclude that DUSP9/MKP-4 is a bona fide target of PKA signaling and that attenuation of DUSP9/MKP-4 function can mediate cross-talk between the PKA pathway and MAPK signaling through both ERK1/2 and p38α in vivo.     

Two clusters of residues at the docking groove of mitogen-activated protein kinases differentially mediate their functional interaction with the tyrosine phosphatases PTP-SL and STEP.

Regulated function of mitogen-activated protein (MAP) kinases involves their selective association through docking sites with both activating MAP kinase kinases and inactivating phosphatases, including dual specificity and protein-tyrosine phosphatases (PTP). Site-directed mutagenesis on the mammalian MAP kinases ERK2 and p38alpha identified within their C-terminal docking grooves two clusters of residues important for association with their regulatory PTPs, PTP-SL and STEP. ERK2 and p38alpha mutations that resembled the sevenmaker gain-of-function mutation in the Rolled D. melanogaster ERK2 homologue failed to associate with PTP-SL, were not retained in the cytosol, and were poorly inactivated by this PTP. Additional ERK2 mutations at the docking groove showed deficient association and dephosphorylation by PTP-SL, although their cytosolic retention was unaffected. Other ERK2 mutations, resembling gain-of-function mutations in the FUS3 yeast ERK2 homologue, associated to PTP-SL and were inactivated normally by this PTP. Our results demonstrate that mutations at distinct regions of the docking groove of ERK2 and p38alpha differentially affect their association and regulation by the PTP-SL and STEP PTPs.