Heterogeneous distribution of functionally important amino acids in brain areas of adult and aging humans

The regional distribution of seven amino acids thought to have inhibitory neurotransmitter or neurotransmitter precursor function—GABA, glycine, taurine, serine, threonine, phenylalanine, and tyrosine—was determined in 52 discrete areas from brain of adult and old humans. Significant heterogeneity was found, with 3- to 16-fold differences in levels in the various regions analyzed. The patterns of distribution were somewhat different from those in the adult or old rat brain. Relatively few changes were seen in old brain. Heterogeneity in distribution has to be taken into account in assessing physiological changes in amino acid levels and metabolism.Special issue dedicated to Dr. Claude Baxter.     

Gelation and Its Related Changes in Amylose Solution

The phase change for an amylose solution in the binary solvent system of dimethylsulfoxide (DMSO) with water was investigated under various conditions from sol to gel. The phase change was determined with measurements of the fluorescent depolarization and other methods by varying the solvent constitution at 25°C, and then varying the temperature at 10% of DMSO concentration.

The phase diagrams obtained with both variables were substantially similar and were also similar to those for an aqueous agarose solution. This similarity in phase diagram suggests a similar gel formation mechanism of amylose to agarose.

It was found that the phase separation point for the amylose solution agreed with the gel formation point and also with the starting point of retrogradation.     

Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction

Reduced dietary methionine intake (0.17% methionine, MR) and calorie restriction (CR) prolong lifespan in male Fischer 344 rats. Although the mechanisms are unclear, both regimens feature lower body weight and reductions in adiposity. Reduced fat deposition in CR is linked to preservation of insulin responsiveness in older animals. These studies examine the relationship between insulin responsiveness and visceral fat in MR and test whether, despite lower food intake observed in MR animals, decreased visceral fat accretion and preservation of insulin sensitivity is not secondary to CR. Accordingly, rats pair fed (pf) control diet (0.86% methinone, CF) to match the food intake of MR for 80 weeks exhibit insulin, glucose, and leptin levels similar to control-fed animals and comparable amounts of visceral fat. Conversely, MR rats show significantly reduced visceral fat compared to CF and PF with concomitant decreases in basal insulin, glucose, and leptin, and increased adiponectin and triiodothyronine. Daily energy expenditure in MR animals significantly exceeds that of both PF and CF. In a separate cohort, insulin responses of older MR animals as measured by oral glucose challenge are similar to young animals. Longitudinal assessments of MR and CF through 112 weeks of age reveal that MR prevents age-associated increases in serum lipids. By 16 weeks, MR animals show a 40% reduction in insulin-like growth factor-1 (IGF-1) that is sustained throughout life; CF IGF-1 levels decline much later, beginning at 112 weeks. Collectively, the results indicate that MR reduces visceral fat and preserves insulin activity in aging rats independent of energy restriction.     

硫化氢抗衰老作用的分子机制

衰老的特征包括蛋白质稳态失衡、氧化损伤积累、干细胞衰竭、细胞间通信改变、慢性炎症和微生态失调等,且与心血管疾病、糖尿病和阿尔茨海默病等常见的增龄性疾病相关。硫化氢(hydrogen sulfide,H₂S)是一种内源性的气体信号分子,在细菌、动物和植物中均存在其相关代谢。众所周知,生理浓度下的H₂S通过对人体蛋白质的硫巯基化修饰调控细胞信号转导,维持内稳态。近年的研究发现,生物体衰老常伴随内源性H₂S产生的减少和蛋白质硫巯基化水平的普遍下降,补充外源性H₂S可抑制其衰老。例如,阿尔兹海默病、老年性重症肌无力、骨质疏松症等衰老相关疾病中,补充H₂S可改善其症状。上述现象提示生理浓度范围的H₂S具有抗衰老作用。本文从抑制氧化应激、抗炎、保护线粒体功能、维持蛋白质稳态和上调自噬等方面总结了H₂S抗衰老的分子机制,并讨论了目前对H₂S抗衰老机制研究存在的问题和未来研究方向,为抗衰老和治疗衰老相关疾病提供新思路。     

硫化氢抗衰老作用的分子机制

衰老的特征包括蛋白质稳态失衡、氧化损伤积累、干细胞衰竭、细胞间通信改变、慢性炎症和微生态失调等,且与心血管疾病、糖尿病和阿尔茨海默病等常见的增龄性疾病相关。硫化氢(hydrogen sulfide,H₂S)是一种内源性的气体信号分子,在细菌、动物和植物中均存在其相关代谢。众所周知,生理浓度下的H₂S通过对人体蛋白质的硫巯基化修饰调控细胞信号转导,维持内稳态。近年的研究发现,生物体衰老常伴随内源性H₂S产生的减少和蛋白质硫巯基化水平的普遍下降,补充外源性H₂S可抑制其衰老。例如,阿尔兹海默病、老年性重症肌无力、骨质疏松症等衰老相关疾病中,补充H₂S可改善其症状。上述现象提示生理浓度范围的H₂S具有抗衰老作用。本文从抑制氧化应激、抗炎、保护线粒体功能、维持蛋白质稳态和上调自噬等方面总结了H₂S抗衰老的分子机制,并讨论了目前对H₂S抗衰老机制研究存在的问题和未来研究方向,为抗衰老和治疗衰老相关疾病提供新思路。     

Enhanced S-adenosyl-l-methionine production in Saccharomyces cerevisiae by spaceflight culture, overexpressing methionine adenosyltransferase and optimizing cultivation

Aims: S‐adenosyl‐l ‐methionine (SAM) is an important biochemical molecule with great potential in the pharmacological and chemotherapeutic fields. In this study, our aims were to enhance SAM production in Saccharomyces cerevisiae. Methods and Results: Through spaceflight culture, a SAM‐accumulating strain, S. cerevisiae H5M147, was isolated and found to produce 86·89% more SAM than its ground control strain H5. Amplified fragment length polymorphism (AFLP) analysis demonstrated that there were genetic variations between strain H5M147 and its ground control. Through recombinant DNA technology, the heterologous gene encoding methionine adenosyltransferase was integrated into the genome of strain H5M147. The recombinant strain H5MR83 was selected because its SAM production was increased by 42·98% when compared to strain H5M147. Furthermore, cultivation conditions were optimized using the one‐factor‐at‐a‐time and Taguchi methods. Under optimal conditions, strain H5MR83 yielded 7·76 g l^?1 of SAM in shake flask, an increase of 536·07% when compared to the strain H5. Furthermore, 9·64 g l^?1 of SAM was produced in fermenter cultivation. Conclusions: A new SAM‐accumulating strain, S. cerevisiae H5MR83, was obtained through spaceflight culture and genetic modification. Under optimal conditions, SAM production was increased to a relative high level in our study. Significance and Impact of the Study: Through comprehensive application of multiple methods including spaceflight culture, genetic modification and optimizing cultivation, the yield of SAM could be increased by 6·4 times compared to that in the control strain H5. The obtained S. cerevisiae H5MR83 produced 7·76 g l^?1 of SAM in the flask cultures, a significant improvement on previously reported results. The SAM production period with S. cerevisiae H5MR83 was 84 h, which is shorter than previously reported results. Saccharomyces cerevisiae H5MR83 has considerable potential for use in industrial applications.     

Physiology of myeloma cells grown in glucose-limited chemostat cultures

A recombinant myeloma NS1-derived clone was grown in chemostat cultures in Dulbecco's MEM/Ham's F12 (1∶1) medium containing various concentrations of glucose, at a dilution rate of 0.028 h⁻¹. Serum-supplemented cultures were virtually glucose-limited at a large range of glucose feed concentrations (0.7–5 mM). True glucose-limited cultures, however, were only established at low glucose supply levels to 1.3 mM at a maximum. In cultures obtained at higher glucose concentrations methionine was shown to be the growth-limiting compound. The pattern derived for serum-free chemostat cultures was similar, except that growth yields on glucose were much lower. Glucose was shown to be the growth-limiting substrate in cultures fed with media containing less than 4.5 mM glucose. Upon supplying glucose at higher concentrations such cultures presumably run into methionine and/or tryptophan limitation.