PTEN regulates AMPA receptor-mediated cell viability in iPS-derived motor neurons

Excitatory transmission in the brain is commonly mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In amyotrophic lateral sclerosis (ALS), AMPA receptors allow cytotoxic levels of calcium into neurons, contributing to motor neuron injury. We have previously shown that oculomotor neurons resistant to the disease process in ALS show reduced AMPA-mediated inward calcium currents compared with vulnerable spinal motor neurons. We have also shown that PTEN (phosphatase and tensin homolog deleted on chromosome 10) knockdown via siRNA promotes motor neuron survival in models of spinal muscular atrophy (SMA) and ALS. It has been reported that inhibition of PTEN attenuates the death of hippocampal neurons post injury by decreasing the effective translocation of the GluR2 subunit into the membrane. In addition, leptin can regulate AMPA receptor trafficking via PTEN inhibition. Thus, we speculate that manipulation of AMPA receptors by PTEN may represent a potential therapeutic strategy for neuroprotective intervention in ALS and other neurodegenerative disorders. To this end, the first step is to establish a fibroblast–iPS–motor neuron in vitro cell model to study AMPA receptor manipulation. Here we report that iPS-derived motor neurons from human fibroblasts express AMPA receptors. PTEN depletion decreases AMPA receptor expression and AMPA-mediated whole-cell currents, resulting in inhibition of AMPA-induced neuronal death in primary cultured and iPS-derived motor neurons. Taken together, our results imply that PTEN depletion may protect motor neurons by inhibition of excitatory transmission that represents a therapeutic strategy of potential benefit for the amelioration of excitotoxicity in ALS and other neurodegenerative disorders

Myrigalone A inhibits Lepidium sativum seed germination by interference with gibberellin metabolism and apoplastic superoxide production required for embryo extension growth and endosperm rupture

Myrica gale L. (sweet gale) fruit leachate contains myrigalone A (MyA), a rare C-methylated dihydrochalcone and putative allelochemical, which is known to be a phytotoxin impeding seedling growth. We found that MyA inhibited Lepidium sativum L. seed germination in a dose-dependent manner. MyA did not affect testa rupture, but inhibited endosperm rupture and the transition to subsequent seedling growth. MyA inhibited micropylar endosperm cap (CAP) weakening and the increase in the growth potential of the radical/hypocotyl region (RAD) of the embryo, both being key processes required for endosperm rupture. We compared the contents of abscisic acid (ABA) and gibberellins in the tissues and found that the major bioactive forms of gibberellin in L. sativum seed tissues were GA4 and GA6, while GA8 and GA13 were abundant inactive metabolites. MyA did not appreciably affect the ABA contents, but severely interfered with gibberellin metabolism and signaling by inhibiting important steps catalyzed by GA3 oxidase, as well as by interfering with the GID1-type gibberellin signaling pathway. The hormonally and developmentally regulated formation of apoplastic superoxide radicals is important for embryo growth. Specific zones within the RAD were associated with accumulation of apoplastic superoxide radicals and endoreduplication indicative of embryo cell extension. MyA negatively affected both of these processes and acted as a scavenger of apoplastic reactive oxygen species. We propose that MyA is an allelochemical with a novel mode of action on seed germination

Embryo growth, testa permeability, and endosperm weakening are major targets for the environmentally regulated inhibition of Lepidium sativum seed germination by myrigalone

Myrigalone A (MyA) is a rare flavonoid in fruit leachates of Myrica gale, a deciduous shrub adapted to flood-prone habitats. As a putative allelochemical it inhibits seed germination and seedling growth. Using Lepidium sativum as a model target species, experiments were conducted to investigate how environmental cues modulate MyA’s interference with key processes of seed germination. Time course analyses of L. sativum testa and endosperm rupture under different light conditions and water potentials were combined with quantifying testa permeability, endosperm weakening, tissue-specific gibberellin (GA) and abscisic acid (ABA) contents, as well as embryo growth and apoplastic superoxide production important for cell expansion growth. Lepidium sativum testa permeability and early water uptake by imbibition is enhanced by MyA. During late germination, MyA inhibits endosperm weakening and embryo growth, both processes required for endosperm rupture. Inhibition of embryo cell expansion by MyA depends on environmental cues, which is evident from the light-modulated severity of the MyA-mediated inhibition of apoplastic superoxide accumulation. Several important key weakening and growth processes during early and late germination are targets for MyA. These effects are modulated by light conditions and ambient water potential. It is speculated that MyA is a soil seed bank-destroying allelochemical that secures the persistence of M. gale in its flood-prone environment

Timing-dependent effects of salicylic acid treatment on phytohormonal changes, ROS regulation, and antioxidant defense in salinized barley (Hordeum vulgare L.)

Cross-talk between exogenous salicylic acid (SA) and endogenous phytohormone pathways affects the antioxidant defense system and its response to salt stress. The study presented here investigated the effects of SA treatment before and during salt stress on the levels of endogenous plant growth regulators in three barley cultivars with different salinity tolerances: Hordeum vulgare L. cvs. Akhisar (sensitive), Erginel (moderate), and Kalayc (tolerant). The cultivars' relative leaf water contents, growth parameters, proline contents, chlorophyll a/b ratios, and lipid peroxidation levels were measured, along with the activities of enzymes involved in detoxifying reactive oxygen species (ROS) including superoxide-dismutase, peroxidase, catalase, ascorbate-peroxidase, and glutathione-reductase. In addition, levels of several endogenous phytohormones (indole-3-acetic-acid, cytokinins, abscisic acid, jasmonic acid, and ethylene) were measured. Barley is known to be more salt tolerant than related plant species. Accordingly, none of the studied cultivars exhibited changes in membrane lipid peroxidation under salt stress. However, they responded differently to salt-stress with respect to their accumulation of phytohormones and antioxidant enzyme activity. The strongest and weakest increases in ABA and proline accumulation were observed in Kalayc and Akhisar, respectively, suggesting that salt-stress was more effectively managed in Kalayc. The effects of exogenous SA treatment depended on both the timing of the treatment and the cultivar to which it was applied. In general, however, where SA helped mitigate salt stress, it appeared to do so by increasing ROS scavenging capacity and antioxidant enzyme activity. SA treatment also induced changes in phytohormone levels, presumably as a consequence of SA-phytohormone salt-stress cross-talk.Internal Grant Agency of Palacky University [IGA_PrF_ 2019_ 020]; European Regional Development Fund-Project Plants as a tool for sustainable global development [CZ. 02.1.01/0.0/0.0/16_019/0000827]This work was supported by the Internal Grant Agency of Palacky University N. IGA_PrF_ 2019_ 020 and from European Regional Development Fund-Project Plants as a tool for sustainable global development (No. CZ. 02.1.01/0.0/0.0/16_019/0000827). We would also like to thank to Sees-editing Ltd., U.K. for English editing of the manuscript.WOS:0005635386000092-s2.0-85089529111PubMed: 3280791