RESUMEN
Neurolathyrism is a unique neurodegeneration disease caused by ß-N-oxalyl-L-α, ß- diaminopropionic (ß-ODAP) present in grass pea seed (Lathyrus stativus L.) and its pathogenetic mechanism is unclear. This issue has become a critical restriction to take full advantage of drought-tolerant grass pea as an elite germplasm resource under climate change. We found that, in a human glioma cell line, ß-ODAP treatment decreased mitochondrial membrane potential, leading to outside release and overfall of Ca2+ from mitochondria to cellular matrix. Increased Ca2+ in cellular matrix activated the pathway of ECM, and brought about the overexpression of ß1 integrin on cytomembrane surface and the phosphorylation of focal adhesion kinase (FAK). The formation of high concentration of FA units on the cell microfilaments further induced overexpression of paxillin, and then inhibited cytoskeleton polymerization. This phenomenon turned to cause serious cell microfilaments distortion and ultimately cytoskeleton collapse. We also conducted qRT-PCR verification on RNA-sequence data using 8 randomly chosen genes of pathway enrichment, and confirmed that the data was statistically reliable. For the first time, we proposed a relatively complete signal pathway to neurolathyrism. This work would help open a new window to cure neurolathyrism, and fully utilize grass pea germplasm resource under climate change.
Asunto(s)
Aminoácidos Diaminos/farmacología , Adhesiones Focales/efectos de los fármacos , Adhesiones Focales/metabolismo , Integrina beta1/metabolismo , Toxinas Biológicas/farmacología , Calcio/metabolismo , Línea Celular , Biología Computacional/métodos , Citoesqueleto/metabolismo , Matriz Extracelular , Adhesiones Focales/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Integrina beta1/genética , Latirismo/etiología , Latirismo/metabolismo , Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Multimerización de Proteína , Reproducibilidad de los Resultados , Transducción de Señal/efectos de los fármacos , TranscriptomaRESUMEN
Grass pea (Lathyrus sativus L.) cultivation is limited because of the presence in seeds and tissues of the nonprotein amino acid ß-N-oxalyl-L-α,ß-diaminopropionic acid (ß-ODAP), a neurotoxin that can cause lathyrism in humans. Seven grass pea genotypes differing in seed ß-ODAP concentration were grown in pots at three levels of water availability to follow changes in the concentration and amount of ß-ODAP in leaves and pods and seeds. The concentration and amount of ß-ODAP decreased in leaves in early reproductive development and in pods as they matured, while water stress increased ß-ODAP concentration in leaves and pods at these stages. The net amount of ß-ODAP in leaves and pods at early podding was positively associated with seed ß-ODAP concentration at maturity. We conclude that variation among genotypes in seed ß-ODAP concentration results from variation in net accumulation of ß-ODAP in leaves and pods during vegetative and early reproductive development.
Asunto(s)
Aminoácidos Diaminos/metabolismo , Frutas/crecimiento & desarrollo , Lathyrus/metabolismo , Neurotoxinas/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Semillas/metabolismo , Agua/metabolismo , Aminoácidos Diaminos/análisis , Frutas/química , Frutas/genética , Frutas/metabolismo , Genotipo , Lathyrus/química , Lathyrus/genética , Lathyrus/crecimiento & desarrollo , Neurotoxinas/análisis , Hojas de la Planta/química , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Semillas/química , Semillas/genética , Semillas/crecimiento & desarrollo , Agua/análisisRESUMEN
Grass pea (Lathyrus sativus) is a legume with various adverse adaptability and rich nutrition. However, it can lead to the human and animal neurotoxicity after long-term consumption due to its neurotoxin, beta-N-oxalyl-L-alpha, beta-diaminopropionic acid (beta-ODAP), limiting its utilization. This paper summarized the influences of beta-ODAP on osmotic adjustment and growth regulation in grass pea under drought stress, the research progress in analysis methods, toxicological mechanisms and practical utility of beta-ODAP, and the breeding strategies for low- and zero-beta-ODAP. Beta-ODAP synthesis was found to be abundant in grass pea under drought stress and its content was enhanced gradually with the increasing extent of drought stress. beta-ODAP could supply nitrogen for plant growth and seed development, scavenge reactive oxygen species (ROS), involve in osmotic adjustment as a soluble amino acid, transport zinc-ions as a carrier molecule, and impact nodule development. However, increasing the content of sulfur-containing amino acids (methionine and cysteine) could decrease the level of toxicity of grass pea. There were a lot of investigations on collecting genetic resources, cross breeding, tissue culture, and gene manipulation for low- and zero-toxin in grass pea in recent years. Although beta-ODAP could induce excitotoxicity by damaging intracellular Ca2+ homeostasis and as glutamate analogues, it has medicinal value on hemostasis and anti-tumor.