RESUMO
Although previous results showed that exogenous hydrogen (H2) alleviated aluminum (Al) toxicity, the detailed mechanism remains unclear. Here, we reported that the exposure of germinating rice seeds to Al triggered H2 production, followed by a decrease of GA/ABA ratio and seed germination inhibition. Compared to inert gas (argon), H2 pretreatment not only strengthened H2 production and alleviated Al-induced germination inhibition, but also partially reestablished the balance between GA and ABA. By contrast, a GA biosynthesis inhibitor paclobutrazol (PAC) could block the H2-alleviated germination inhibition. The expression of GA biosynthesis genes (GA20ox1 and GA20ox2) and ABA catabolism genes (ABA8ox1 and ABA8ox2), was also induced by H2. Above results indicated that GA/ABA might be partially involved in H2 responses. Subsequent results revealed that compared with Al alone, transcripts of miR398a and miR159a were decreased by H2, and expression levels of their target genes OsSOD2 and OsGAMYB were up-regulated. Whereas, miR528 and miR160a transcripts were increased differentially, and contrasting tendencies were observed in the changes of their target genes (OsAO and OsARF10). The transcripts of Al-tolerant gene OsSTAR1/OsSTAR2 and OsFRDL4 were up-regulated. Above results were consistent with the anti-oxidant defense, decreased Al accumulation, and enhanced citrate efflux. Together, our results provided insight into the mechanism underlying H2-triggered Al tolerance in plants.
Assuntos
Ácido Abscísico/genética , Alumínio/toxicidade , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Germinação/efeitos dos fármacos , Giberelinas/genética , Hidrogênio/farmacologia , Oryza/crescimento & desenvolvimento , Poluentes do Solo/toxicidade , Ácido Abscísico/biossíntese , Alumínio/metabolismo , Genes de Plantas , Giberelinas/biossíntese , Hidrogênio/análise , MicroRNAs/genética , Oryza/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Poluentes do Solo/metabolismoRESUMO
Human amniotic epithelial cells (hAECs) have been reported to have neuroprotective roles in Parkinson's disease (PD) animal models. However, the molecular mechanism is not fully understood. The present study was designed to explore the possible mechanism by which hAECs ameliorate PD symptoms and the important paracrine factors produced by hAECs that attribute to the recovery of dopaminergic neurons. Thus, we performed in vivo and in vitro experiments with hAECs in PD models or lesioned dopaminergic neurons, respectively. First, hAECs were transplanted into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and motor deficits were significantly attenuated. Second, the grafts prevented the loss of nigral dopaminergic neurons and promoted the outgrowth of neurites and striatal axon fibers in PD mice. In addition, decreased microglial activation, inflammatory factor levels and MPTP-induced excessive reactive oxygen species (ROS) levels were also observed in hAEC-treated PD mice. In vitro, we found that the conditioned medium (CM) from hAECs promoted the survival of mesencephalic dopaminergic neurons stimulated with 1-methyl-4-phenylpyridine (MPP+) and induced neurite outgrowth. Next, analysis of hAEC-CM with an antibody array of 507 soluble target proteins revealed that the levels of many neurotrophic factors, growth factors, neuronal cell adhesion molecule (NrCAM) and anti-inflammatory factors were evidently high. In addition, antibody neutralization experiments showed that many of these factors contributed to the survival and growth of dopaminergic neurons and neurite outgrowth. More importantly, we found that the anti-inflammatory factor interleukin-1 receptor antagonist (IL-1ra) also augmented the survival of dopaminergic neurons, demonstrating for the first time an anti-oxidative and anti-inflammatory role of hAECs in PD mice, which represents a novel molecular mechanism of hAECs in the treatment of PD. The molecular mechanism of hAECs recovering lesioned dopaminergic neurons and attenuating PD symptoms. First, hAECs secret many neurotrophic factors, growth factors, and neuronal cell adhesion molecule (NrCAM) which promote the growth of the damaged dopaminergic neurons and their neurites. Second, hAECs produce many anti-inflammatory factors and other factors contributing to reducing the activation of microglia and suppressing the neuroinflammation. Third, hAECs reduce the excessive ROS levels by upregulating some anti-oxidative signals.
Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Anti-Inflamatórios , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Células Epiteliais , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Microglia , Doenças Neuroinflamatórias , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/terapiaRESUMO
Despite recent advances in neurosurgery and pharmaceuticals, contemporary treatments are ineffective in restoring lost neurological functions in patients with injuries and disorders of the central nervous system (CNS). Therefore, novel and effective therapies are urgently needed. Recent studies have indicated that stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), could repair/replace damaged or degenerative neurons and improve functional recovery in both preclinical and clinical trials. However, there are many unanswered questions and unsolved issues regarding stem cell therapy in terms of potency, stability, oncogenicity, immune response, cell sources, and ethics. Currently, human amniotic epithelial cells (hAECs) derived from the amnion exhibit considerable advantages over other stem cells and have drawn much attention from researchers. hAECs are readily available, pose no ethical concerns, and have little risk of tumorigenicity and immunogenicity. Mounting evidence has shown that hAECs can promote neural cell survival and regeneration, repair affected neurons, and reestablish damaged neural connections. It is suggested that hAECs may be the most promising candidate for cell-based therapy of neurological diseases. In this review, we mainly focus on recent advances and potential applications of hAECs for treating various CNS injuries and neurodegenerative disorders. We also discuss current hurdles and challenges regarding hAEC therapies.