ω-6 Polyunsaturated fatty acids (linoleic acid) activate both autophagy and antioxidation in a synergistic feedback loop via TOR-dependent and TOR-independent signaling pathways
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Abstract ω-6 Polyunsaturated fatty acids (PUFAs) are essential fatty acids that participate in macroautophagy (hereafter referred to as autophagy) and the Kelch ECH-associating protein 1 (Keap1)—nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant system in organisms. However, the molecular mechanisms by which ω-6 PUFAs (linoleic acid) regulate autophagy and Keap1–Nrf2 antioxidant system are not completely understood. Therefore, the purposes of this study were to explore the molecular mechanisms by which ω-6 PUFAs (linoleic acid) regulate autophagy and antioxidant system and to investigate the potential relationship between autophagy and antioxidant system through transcriptomic analysis, quantitative real-time polymerase chain reaction (RT-qPCR), western blot analysis, coimmunoprecipitation (Co-IP) and electrophoretic mobility shift assays (EMSAs) in vivo and in vitro. The results of the present study indicated that ω-6 PUFAs in diets induced autophagy but decrease antioxidant ability in vivo. However, the results also provided evidence, for the first time, that ω-6 PUFAs (linoleic acid) induced autophagy and increased antioxidant ability through the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and the AMPK-target of rapamycin (TOR) signaling pathway in hepatocytes in vitro. Interestingly, the findings revealed a ω-6 PUFA-induced synergistic feedback loop between autophagy and antioxidant system, which are connected with each other through the P62 and Keap1 complex. These results suggested that ω-6 PUFAs (linoleic acid) could be useful for activating a synergistic feedback loop between autophagy and antioxidant system and could greatly aid in the prevention and treatment of multiple pathologies.Keywords:
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In order to explore the fatty acid distribution characteristics of wheat grain,the fatty acid contents in grain whole-mills of 97 common wheat cultivars/lines were determined by gas chromatography.The results show that,the mean values of total fatty acid content,palmitic(C16∶0),stearic acid(C18∶0),oleic acid(C18∶1),linoleic acid(C18∶2) and linolenic acid(C18∶3) were 1.91%,0.37%,0.02%,0.27%,1.17% and 0.08%,respectively.The content of unsaturated fatty acid(Oleic acid,Linoleic acid and Linolenic acid) was up to 79%.Every kinds of fatty acid fits normal distribution in these wheat grain samples with wide variations.The total fatty acid content was significant correlation with the content of palmitic acid,stearic acid,oleic acid or linoleie acid,respectively.Those results provide a base reference to further improve and utilize the wheat grain fatty acids.
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AbstractIt has been reported in various model organisms that autophagy and the target of rapamycin complex 1 (TORC1) signaling are strongly involved in eukaryotic cell aging and decreasing TORC1 activity extends longevity by an autophagy-dependent mechanism. Thus, to expand our knowledge of the regulation of eukaryotic cell aging, it is important to understand the relationship between TORC1 signaling and autophagy. Many researchers have shown that TORC1 represses autophagy under normal growth conditions, and TORC1 inactivation contributes to the upregulation of autophagy. However, it is poorly understood how autophagy is regulated or terminated when starvation is prolonged. Here, we report that bidirectional regulation between autophagy and TORC1 exists in the yeast Saccharomyces cerevisiae. We show that mutant cells with weak TORC1 activity maintain autophagy longer than wild-type cells, and TORC1 is partially reactivated under ongoing nitrogen starvation by an autophagy-dependent mechanism. In addition, we found that Atg13 is gradually rephosphorylated during prolonged nitrogen starvation, and the kinase activity of Atg1 is required for Atg13 rephosphorylation. Our data suggest that TORC1 can be substantially, if not fully, reactivated in an autophagy-dependent manner under ongoing starvation, and that partially reactivated TORC1 eventually plays a role in the attenuation of autophagy.
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Abstract: Polyunsaturated fatty acids are needed for normal neonatal brain development, but the degree of conversion of the 18‐carbon polyunsaturated fatty acid precursors consumed in the diet to their respective 20‐and 22‐carbon polyunsaturates accumulating in the brain is not well known. In the present study, in vivo 13 C nuclear magnetic resonance spectroscopy was used to monitor noninvasively the brain uptake and metabolism of a mixture of uniformly 13 C‐enriched 16‐and 18‐carbon polyunsaturated fatty acid methyl esters injected intragastrically into neonatal rats. In vivo NMR spectra of the rat brain at postnatal days 10 and 17 had larger fatty acid signals than in uninjected controls, but changes in levels of individual fatty acids could not be distinguished. One day after injection of the U‐ 13 C‐polyunsaturated fatty acid mixture, 13 C enrichment (measured by isotope ratio mass spectrometry) was similar in brain phospholipids, free fatty acids, free cholesterol, and brain aqueous extract; 13 C enrichment remained high in the phospholipids and cholesterol for 15 days. 13 C enrichment was similar in the main fatty acids of the brain within 1 day of injection but 15 days later had declined in all except arachidonic acid while continuing to increase in docosahexaenoic acid. These changes in 13 C enrichment in brain fatty acids paralleled the developmental changes in brain fatty acid composition. We conclude that, in the neonatal rat brain, dietary 16‐and 18‐carbon polyunsaturates are not only elongated and desaturated but are also utilized for de novo synthesis of long‐chain saturated and monounsaturated fatty acids and cholesterol.
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macroautophagy 的角色(此后 autophagy ) 在癌症，到临床的干预的生物学和反应是复杂的。autophagy 是在许多肿瘤背景的 dysregulated，是清楚的，在肿瘤开始和前进期间，并且响应治疗。然而，在控制房间行为的 autophagy 的多种的机械学的角色使在一个给定的肿瘤背景预言困难 autophagy 的角色，并且，由扩展，指向 autophagy 的治疗学的结果，力量。在这评论，我们在在癌症支持 pro-tumorigenic 和 anti-tumorigenic 和 autophagy 的治疗学的角色的文学总结证据。这概述在滋养的管理，房间死亡，房间老朽， proteotoxic 应力的规定和细胞的动态平衡包含 autophagy 的角色，在在新陈代谢的变化的肿瘤主人相互作用和参予的规定。在可能的地方，我们也试着理解，为 autophagy 的这些角色的机械学的底。我们明确地阐述在在 vivo.We 使这些问题清楚些的癌症的模型也考虑 autophagy 蛋白质的任何东西或上述所有函数怎么可能是可指向的由的遗传上设计的老鼠的新兴的角色现存或 pharmacologic 代理人的未来类。我们由简短在细胞的过程为关键 autophagy 蛋白质的子集探索不在经典中的角色得出结论，并且这些怎么可能在癌症之上影响。
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Autophagy is a ubiquitous, non-selective degradation process in eukaryotic cells that is conserved from yeast to man. Autophagy research has increased significantly in the last ten years, as autophagy has been connected with cancer, neurodegenerative disease and various human developmental processes. Autophagy also appears to play an important role in filamentous fungi, impacting growth, morphology and development. In this review, an autophagy model developed for the Aspergillus fumigatus is used as an intellectual framework to discuss autophagy in filamentous fungi. Studies imply that, similar to yeast, fungal autophagy is characterized by the presence of autophagosomes and controlled by the target of rapamycin (Tor) kinase. Autophagy is highly regulated and is under the control of a number of signaling pathways, including the Tor pathway, which coordinates cell growth with nutrient availability. The data shows that autophagy in A.fumigatus is also controlled by the cAMP-dependent protein kinase (PKA) pathway. Elevated levels of PKA activity inhibited autophagy and inactivation of the PKA pathway is sufficient to induce a robust autophagy response. In addition, fungal autophagy is apparently involved in protection against cell death and has significant effects on cellular growth and development. However, the only two putative autophagy proteins characterized in filamentous fungi are Atg1 and Atg8. Here we will discuss various strategies used to study and monitor fungal autophagy as well as the possible relationship between autophagy, physiology, and morphological development.
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Autophagy 是导致长寿蛋白质和不正常的细胞器的降级的高度调整的细胞的机制。这个过程处于与神经病学的疾病相关的许多生理、病理学的条件被含有。最近的研究证明在服的局部缺血的 autophagy 的存在，而是没有一致还处于这个条件关于 autophagy 的功能被到达了。这篇文章在服的局部缺血或灌注期间加亮 autophagy 的激活，特别在神经原和星形细胞，以及在 neuronal 或 astrocytic 房间死亡和幸存的 autophagy 的角色。我们建议那 autophagy 的生理的层次，大概引起了由对谦虚组织缺氧或局部缺血温和，看起来保护。然而，严重组织缺氧或局部缺血或灌注引起的 autophagy 的高水平可以引起自我消化和最终的 neuronal 和 astrocytic 房间死亡。我们也讨论那氧化并且 endoplasmic 蜂窝胃(嗯) 在服的组织缺氧或局部缺血或灌注的压力是在神经原和星形细胞的 autophagy 的有势力刺激。另外，我们考察一方面建议在 autophagy 之间的可观的重叠的证据，和 apoptosis，坏死和 necroptosis 在另一方面，在决定结果和损坏神经原和星形细胞的最后的形态学。
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