Efficiency of ademethionine in oxidative stress in tissues of irradiated rats

Introduction. Ionizing radiation in low doses of low intensity causes prolonged activation of lipid per oxidation and depletion of the antioxidant system in a living organism. Moreover, Ademethionine is currently being considered as a promising antioxidant.Method. Experimental studies were carried out on 60 sexually mature male Wistar rats. The animals were irradiated in a total dose of 1Gy on a γ-therapeutic device AGAT-R No. 83 (isotope 60Co). At the end of the total dose, the rats were injected intraperitoneally with Heptral (ademethionine) after 15 minutes, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 hours after radiation exposure at the rate of 10 mg / kg mass. After the introduction of Heptral, the animals were taken into the experiment after 24 hours, 3, 7, 15 days. In homogenates of the spleen and thymus of animals, the amount of oxidized and reduced forms of pyridine nucleotides was determined.Results. Chronic γ-irradiation in a total dose of 1Gy leads to a significant decrease in the content of reduced forms of pyridine nucleotides in the spleen and thymus of rats. Administration of Heptral to irradiated animals normalized oxidative homeostasis. So, on the 7th day of the experiment, the amount of oxidized forms of pyridine nucleotides in the spleen was 47.3% lower, and reduced - 36.3% higher than in animals that did not receive treatment. At the end of the observation period, the reduction coefficient of pyridine nucleotides in the spleen slightly differed from the control level. In comparison with irradiated animals, which were not injected with Heptral, the NADP content was lower by 70.3%, and NADPH2 - higher by 48.8%.Conclusion. The course administration of Heptral to irradiated animals leads to the normalization of the reduction factor of pyridine nucleotides. According to its mechanism of action, Heptral can be used in the complex treatment of low- intensity radiation injuries in low doses.

Nicotinamide Effectively Suppresses Fusarium Head Blight in Wheat Plants

Pyridine nucleotides such as a nicotinamide adenine dinucleotide (NAD) are known as plant defense activators. We previously reported that nicotinamide mononucleotide (NMN) enhanced disease resistance against fungal pathogen Fusarium graminearum in barley and Arabidopsis. In this study, we reveal that the pretreatment of nicotinamide (NIM), which does not contain nucleotides, effectively suppresses disease development of Fusarium Head Blight (FHB) in wheat plants. Correspondingly, deoxynivalenol (DON) mycotoxin accumulation was also significantly decreased by NIM pretreatment. A metabolome analysis showed that several antioxidant and antifungal compounds such as trigonelline were significantly accumulated in the NIM-pretreated spikes after inoculation of F. graminearum. In addition, some metabolites involved in the DNA hypomethylation were accumulated in the NIM-pretreated spikes. On the other hand, fungal metabolites DON and ergosterol peroxide were significantly reduced by the NIM pretreatment. Since NIM is relative stable and inexpensive compared with NMN and NAD, it may be more useful for the control of symptoms of FHB and DON accumulation in wheat and other crops.

Combination of Copper Ions and Nucleotide Generates Aggregates from Prion Protein Fragments in the N-Terminal Domain

Background: It has been previously found that PrP23-98, which contains four highly conserved octarepeats (residues 60-91) and one partial repeat (residues 92-96), polymerizes into amyloid-like and proteinase K-resistant spherical aggregates in the presence of NADPH plus copper ions. Objective: We aimed to determine the requirements for the formation of these aggregates. Methods: In this study, we performed an aggregation experiment using N-acetylated and Camidated PrP fragments of the N-terminal domain, Octa1, Octa2, Octa3, Octa4, PrP84−114, and PrP76−114, in the presence of NADPH with copper ions, and focused on the effect of the number of copper-binding sites on aggregation. Results: Among these PrP fragments, Octa4, containing four copper-binding sites, was particularly effective in forming aggregates. We also tested the effect of other pyridine nucleotides and adenine nucleotides on the aggregation of Octa4. ATP was equally effective, but NADH, NADP, ADP, and AMP had no effect. Conclusion: The phosphate group on the adenine-linked ribose moiety of adenine nucleotides and pyridine nucleotides is presumed to be essential for the observed effect on aggregation. Efficient aggregation requires the presence of the four octarepeats. These insights may be helpful in the eventual development of therapeutic agents against prion-related disorders.

Redox Components: Key Regulators of Epigenetic Modifications in Plants

Epigenetic modifications including DNA methylation, histone modifications, and chromatin remodeling are crucial regulators of chromatin architecture and gene expression in plants. Their dynamics are significantly influenced by oxidants, such as reactive oxygen species (ROS) and nitric oxide (NO), and antioxidants, like pyridine nucleotides and glutathione in plants. These redox intermediates regulate the activities and expression of many enzymes involved in DNA methylation, histone methylation and acetylation, and chromatin remodeling, consequently controlling plant growth and development, and responses to diverse environmental stresses. In recent years, much progress has been made in understanding the functional mechanisms of epigenetic modifications and the roles of redox mediators in controlling gene expression in plants. However, the integrated view of the mechanisms for redox regulation of the epigenetic marks is limited. In this review, we summarize recent advances on the roles and mechanisms of redox components in regulating multiple epigenetic modifications, with a focus of the functions of ROS, NO, and multiple antioxidants in plants.

Extracellular pyridine nucleotides trigger plant systemic immunity through a lectin receptor kinase/BAK1 complex

Systemic acquired resistance (SAR) is a long-lasting broad-spectrum plant immunity induced by mobile signals produced in the local leaves where the initial infection occurs. Although multiple structurally unrelated signals have been proposed, the mechanisms responsible for perception of these signals in the systemic leaves are unknown. Here, we show that exogenously applied nicotinamide adenine dinucleotide (NAD+) moves systemically and induces systemic immunity. We demonstrate that the lectin receptor kinase (LecRK), LecRK-VI.2, is a potential receptor for extracellular NAD+ (eNAD+) and NAD+ phosphate (eNADP+) and plays a central role in biological induction of SAR. LecRK-VI.2 constitutively associates with BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE1 (BAK1) in vivo. Furthermore, BAK1 and its homolog BAK1-LIKE1 are required for eNAD(P)+ signaling and SAR, and the kinase activities of LecR-VI.2 and BAK1 are indispensable to their function in SAR. Our results indicate that eNAD+ is a putative mobile signal, which triggers SAR through its receptor complex LecRK-VI.2/BAK1 in Arabidopsis thaliana.

Nicotinamide adenine dinucleotide is transported into mammalian mitochondria

Mitochondrial NAD levels influence fuel selection, circadian rhythms, and cell survival under stress. It has alternately been argued that NAD in mammalian mitochondria arises from import of cytosolic nicotinamide (NAM), nicotinamide mononucleotide (NMN), or NAD itself. We provide evidence that murine and human mitochondria take up intact NAD. Isolated mitochondria preparations cannot make NAD from NAM, and while NAD is synthesized from NMN, it does not localize to the mitochondrial matrix or effectively support oxidative phosphorylation. Treating cells with nicotinamide riboside that is isotopically labeled on the nicotinamide and ribose moieties results in the appearance of doubly labeled NAD within mitochondria. Analogous experiments with doubly labeled nicotinic acid riboside (labeling cytosolic NAD without labeling NMN) demonstrate that NAD(H) is the imported species. Our results challenge the long-held view that the mitochondrial inner membrane is impermeable to pyridine nucleotides and suggest the existence of an unrecognized mammalian NAD (or NADH) transporter.