低氧与铁代谢相关蛋白

氧和铁这两种元素对生命活动十分重要. 低氧诱导因子(hypoxia-inducible factors, HIFs)作为转录因子,参与一系列靶基因的表达调控以适应低氧. 铁参与 DNA合成、氧气运输、代谢反应等多种细胞活动,过量游离铁会通过Haber-Weiss或 Fenton反应产生毒性自由基. 细胞通过与铁吸收、存储和利用有关的多种铁代谢相 关蛋白之间的协同作用来维持铁稳态. 与铁稳态相关的一些基因是HIFs的靶基因或 者间接受低氧调控,包括转铁蛋白、转铁蛋白受体、二价金属转运体1、铁调素、膜 铁转运蛋白、血浆铜蓝蛋白、铁蛋白等,而胞内铁浓度的改变能影响HIFs的表达. 本文就低氧与铁代谢相关蛋白的关系,尤其是低氧对铁代谢相关蛋白的调节作一综 述.     

卵巢低氧微环境调节哺乳动物排卵的分子机制

哺乳动物排卵过程复杂,包括卵泡发育、卵泡成熟破裂后的排卵以及黄体形成和退化等过程。目前研究表明,排卵过程受低氧微环境和响应低氧条件的因子-低氧诱导因子(Hypoxic inducible factor, HIF)的影响。低氧调控HIF并影响许多生理过程,如血管生成、炎症反应等。尽管排卵的具体过程早已阐明,但低氧参与调控排卵过程的分子机制并不十分清楚。本文主要综述了哺乳动物在排卵过程中低氧环境如何产生以及HIF如何调控该过程的分子机制,旨在进一步理解排卵机制和卵巢的综合性功能,为相关的卵巢疾病提供一定的理论依据。     

内质网应激与哺乳动物雄性生殖

内质网应激 (endoplasmic reticulum stress,ERS) 激活未折叠蛋白反应,维持哺乳动物细胞的胞内稳态,过度持续的ERS导致细胞凋亡。最新研究表明,ERS对哺乳动物雄性生殖有重要的调节作用,包括对精母细胞、睾丸结构及精子发生的影响。ERS是研究生殖细胞生存和凋亡的新通路。雄性不育可能是由过度ERS引起的。本文通过简述ERS的最新研究进展,分析雄性生殖与ERS的关系,并从ERS调控雄性生殖角度提出新的理解和展望。     

低氧对脂肪细胞发育及脂质代谢调控研究进展

脂肪细胞的生长、分化与增殖贯穿整个生命过程,脂肪细胞中脂质代谢紊乱影响脂肪组织免疫和全身能量代谢。脂质代谢参与调控机体多种疾病的发生与发展,如高脂血症、非酒精性脂肪肝病、糖尿病和癌症等,对人和动物健康具有重大威胁。低氧诱导因子（hypoxia inducible factor,HIF）是介导机体组织器官中氧感受器的主要转录因子,HIF可调控脂质合成、脂肪酸代谢和脂滴形成并诱导疾病发生。但由于低氧程度、时间和作用方式的不同,对机体脂肪细胞发育和脂质代谢产生有害或有益的影响还无从定论。本文总结了低氧介导转录因子的调控作用以及对脂肪细胞发育和脂质代谢调控的研究进展,旨在揭示低氧诱导脂肪细胞代谢途径变化的潜在机制。     

Sestrins参与调解代谢稳态相关机制的研究进展

Sestrins是一类进化上保守的蛋白质家族,它们作为代谢稳态的重要调节剂,抑制氧化应激,参与一磷酸腺苷激活的蛋白激酶(AMPK)-哺乳动物雷帕霉素靶点(m TOR)信号通路等重要活动。在脊椎动物中,Sestrin基因失活导致氧化损伤,脂肪堆积,线粒体功能障碍,肌肉变性等加速组织衰老的多种代谢病理状态。近年来,Sestrins调节代谢和对抗衰老的功能及机制已被越来越多的研究结果发现和证实。然而其确切作用机制尚不明确。因此,对Sestrins功能和调节机制的深入研究将会给与代谢、衰老相关的疾病,例如糖尿病、癌症提供新的治疗理念。     

横断山区三种小型哺乳动物代谢特征的研究进展

代谢率是生理生态学中的重要指标,能反映不同物种和个体之间的能量消耗水平,在动物适应环境的过程中具有重要的意义,各种不同的物理和生物因素都可能影响到动物的代谢特征。本文综述了体重和温度对横断山区小型哺乳动物中缅树鼩、大绒鼠和高山姬鼠代谢率的影响,比较了3种小型哺乳动物与其它地区小型哺乳动物的异同点,并给出了横断山区小型哺乳动物特殊的一些代谢特征。最后,通过比较代谢产热特征探讨了中缅树鼩的起源问题。     

不同低氧暴露对大鼠有氧代谢潜能的影响

目的:同时从血液运氧能力和骨骼肌氧化能力的角度,观察不同低氧暴露对机体有氧代谢潜能的影响。方法:雄性SD大鼠30只,随机分成3组(n=10):常氧对照组、12h低氧暴露组(间歇低氧暴露组)和24h低氧暴露组(持续低氧暴露组)。氧浓度为13.6%。6周后测试红细胞(RBC)、血红蛋白(Hb)、红细胞压积(Hct)、2,3-二磷酸甘油酸(2,3-DPG)和腓肠肌柠檬酸合成酶(CS)、琥珀酸脱氢酶(SDH)、苹果酸脱氢酶(MDH)活性。结果:持续低氧能显著提高RBC、Hb、Hct、2,3-DPG和腓肠肌CS、SDH、MDH活性;间歇低氧除了显著提高Hb外,其它指标无明显变化。结论:持续低氧暴露同时提高机体运氧能力和骨骼肌氧化能力,可以充分提高机体有氧代谢潜能;间歇低氧暴露只能提高血氧容量,对血氧亲和力和骨骼肌氧化能力没有影响,提高机体有氧代谢潜能的效果不如持续低氧暴露。     

体外培养的哺乳动物细胞的葡萄糖和谷氨酰胺代谢

综述体外培养哺乳动物细胞的葡萄糖和谷氨酰胺代谢。大部分的葡萄糖通过糖酵解途径为细胞提供中间代谢物质和能量 ,最终生成乳酸 ,只有很少部分进入TCA循环和磷酸戊糖途径。谷氨酰胺通过谷氨酰胺酶生成谷氨酸 ,并进一步通过谷氨酸脱氢酶或转氨酶生成α -酮戊二酸进入TCA循环 ,为细胞提供中间代谢物质和能量。糖酵解和谷氨酰胺代谢 (glutaminolysis)受葡萄糖和谷氨酰胺的影响而相互调节。     

间歇性低氧对小白鼠营养代谢的影响

目的：探讨间歇性低氧对营养代谢功能的影响。方法：健康小白鼠随机分为正常、正常低氧、高脂、高脂低氧。通过17d的喂养和低氧训练,测量动物的体重、血糖、血胆固醇含量的变化及肝脏组织切片。结果：经间歇性低氧处理明显抑制高脂高糖饲养导致的体重、血糖、血胆固醇增高,肝脏脂肪细胞分布的密度和范围均比单纯高脂组有所降低。结论：适度的间歇性低氧可以降低血糖以及血液中胆固醇的水平,减轻体重,并可以有效防止肝细胞脂肪变性。     

哺乳动物性别决定基因的研究进展

哺乳动物的性别发育经历了个连续不同时期;受精时期性染色体的构建（XY或XX）;性腺发育和分化（精巢或卵巢）;获得恰当的性别表现型（雄性或雌性）。人们已经发现睾丸决定因子（Testis determining factor）就是SRY（Sex determining region on Y chromosome）,并逐渐确定了其他与性别决定和性别反转相关的基因,如SOX9,DAX1,SF1,WT1,GATA-4等。综述了与哺乳动物性别控制有关的基因研究进展。     

环境胁迫下内生菌与宿主代谢相互作用研究进展

植物体内成分是实时反映其生理状态的最直接指标,是其遭受生物或非生物胁迫应激状态的体现,微生物与植物的共生抗逆亦由代谢的重置与调控得以实现.内生菌可以自身细胞功能或代谢产物调控宿主代谢,其自身可产生独特的、显著区别于宿主的代谢成分参与抗逆;而宿主内环境的长期“驯化”亦可改变内生菌的表型和代谢.较全面地分析了植物与微生物共...     

部分水产养殖动物性别控制基因的研究进展

动物的性别是受遗传或环境等因素控制的。自从在哺乳动物中发现了性别决定基因SRY后,还发现了许多其他与性别控制和性腺发育相关的基因。由于海水养殖动物的性别控制技术在遗传育种和生产中十分重要,因此利用现代分子生物技术研究性别控制的基因成为热点。本文综述了鱼类、锯缘青蟹、海龟和海胆等水产养殖动物性别控制基因的研究进展。     

O3浓度升高对植物活性氧代谢系统影响的研究进展

为了揭示臭氧（O3）浓度升高对植物活性氧代谢系统的影响机理,从代谢生理角度,总结了近年来国内外关于臭氧浓度升高对植物活性氧自由基代谢速率、细胞膜脂过氧化程度、抗氧化系统及生物量和产量影响的研究进展,同时,就臭氧浓度升高与二氧化碳浓度升高的复合作用对植物活性氧代谢系统的影响,及阐明二者相互作用对植物抗氧化系统影响机理的研究进行了综述。在此基础上指出在未来研究中,要在分子水平上进一步深入研究植物活性氧代谢系统对高浓度臭氧、二氧化碳复合作用的响应机理,并应加强高浓度二氧化碳对臭氧胁迫下植物抗氧化系统影响的研究,为解决如何减轻臭氧浓度升高对植物造成的氧化伤害提供基础理论依据。     

Influence of Age on Stress Responses to Metabolic Cage Housing in Rats

1.We studied the effect of isolation stress in 3- and 12-month-old rats individually housed in metabolic cages for 7 days. Urine (24 hr) was collected daily from one group of animals of each age. The other group was tested in an open field and on a hot plate on days 1 and 7.2.Total deambulation in the open-field test was lower in young than in older rats both on day 1 (54.7 ± 9.9 vs 80 ± 8.9 crossings/session; P < 0.04) and on day 7 (21 ± 9 vs 48 ± 7 crossings per session; P < 0.04) and decreased significantly in the two groups when tested on day 7 (P < 0.03). Latency to paw-licking in the hot-plate test was longer in young than in older animals on day 1 (14 ± 2 vs 8 ± 4 sec; P < 0.05) but was similar in the two groups on day 7.3.Urinary excretions of norepinephrine (NE) and epinephrine (E) were determined by HPLC with electrochemical detection. Urinary NE in day 1 was similar in young and older animals (2627 ± 828 vs 3069 ± 598 ng/24 hr). In young animals NE excretion decreased along the study and was significantly (P < 0.02) lower than on day 1 during the last 3 days of the study. Conversely, in older animals urinary excretion of NE remained similar throughout the study. On day 7 urinary excretion of NE in older animals was about two fold that in young rats. Urinary E was similar in young and older rats (341 ± 127 vs 532 ± 256 ng/24 hr) on day 1 and showed a tendency to increase throughout the study.4.Urinary monoamine oxidase inhibitory (IMAO) activity was determined by testing the ability of urine extracts to inhibit rat liver MAO activity in vitro and was higher in young than in older animals throughout the study (day 1, 54.8 ± 4.2 vs 25.1 ± 5.1%; P < 0.02). In young rats excretion of IMAO was significantly higher during the last 3 days of the study than on day 1 (P < 0.05). In older animals urinary IMAO showed a tendency to increase at the end of the study.5.Isolation stress caused by housing rats in metabolic cages results in different behavioral and metabolic responses in young and older animals. Young animals exhibit a lower locomotor and analgesic response and excrete lower amounts of NE and higher IMAO activity in the urine than older rats. The metabolic and behavioral responses to isolation stress are highly dependent on the age of the animals tested. These results should be taken into consideration when designing experiments requiring the use of metabolic cages.     

Metabolic flux analysis of CHO cell metabolism in the late non‐growth phase

Chinese hamster ovary (CHO) cell cultures are commonly used for production of recombinant human therapeutic proteins. Often the goal of such a process is to separate the growth phase of the cells, from the non‐growth phase where ideally the cells are diverting resources to produce the protein of interest. Characterizing the way that the cells use nutrients in terms of metabolic fluxes as a function of culture conditions can provide a deeper understanding of the cell biology offering guidance for process improvements. To evaluate the fluxes, metabolic flux analysis of the CHO cell culture in the non‐growth phase was performed by a combination of steady‐state isotopomer balancing and stoichiometric modeling. Analysis of the glycolytic pathway and pentose phosphate pathway (PPP) indicated that almost all of the consumed glucose is diverted towards PPP with a high NADPH production; with even recycle from PPP to G6P in some cases. Almost all of the pyruvate produced from glycolysis entered the TCA cycle with little or no lactate production. Comparison of the non‐growth phase against previously reported fluxes from growth phase cultures indicated marked differences in the fluxes, in terms of the split between glycolysis and PPP, and also around the pyruvate node. Possible reasons for the high NADPH production are also discussed. Evaluation of the fluxes indicated that the medium strength, carbon dioxide level, and temperature with dissolved oxygen have statistically significant impacts on different nodes of the flux network. Biotechnol. Bioeng. 2011; 108:82–92. © 2010 Wiley Periodicals, Inc.     

植物非共生血红蛋白的研究进展

植物非共生血红蛋白（nsHb）基因在植物界广泛存在。许多生物和非生物胁迫可以诱导nsHb的表达。nsHb在植物的生长发育和逆境胁迫中具有重要功能,其作用机制与NO的代谢密切相关。文章综述了非共生血红蛋白的表达特性、生物学功能及其作用机制等方面的研究进展。     

Metabolic memory: mechanisms and implications for diabetic vasculopathies

In the past decades, a persistent progression of diabetic vascular complications despite reversal of hyperglycemia has been observed in both experimental and clinical studies. This durable effect of prior hyperglycemia on the initiation and progression of diabetic vasculopathies was defined as “metabolic memory”. Subsequently, enhanced glycation of cellular proteins and lipids, sustained oxidative stress, and prolonged inflammation were demonstrated to mediate this phenomenon. Recently, emerging evidence strongly suggests that epigenetic modifications may account for the molecular and phenotypic changes associated with hyperglycemic memory. In this review, we presented an overview on the discovery of metabolic memory, the recent progress in its molecular mechanisms, and the future implications related to its fundamental research and clinical application.     

Hypoxia and its effect on the cellular system

Eukaryotic cells utilize oxygen for different functions of cell organelles owing to cellular survival. A balanced oxygen homeostasis is an essential requirement to maintain the regulation of normal cellular systems. Any changes in the oxygen level are stressful and can alter the expression of different homeostasis regulatory genes and proteins. Lack of oxygen or hypoxia results in oxidative stress and formation of hypoxia inducible factors (HIF) and reactive oxygen species (ROS). Substantial cellular damages due to hypoxia have been reported to play a major role in various pathological conditions. There are different studies which demonstrated that the functions of cellular system are disrupted by hypoxia. Currently, study on cellular effects following hypoxia is an important field of research as it not only helps to decipher different signaling pathway modulation, but also helps to explore novel therapeutic strategies. On the basis of the beneficial effect of hypoxia preconditioning of cellular organelles, many therapeutic investigations are ongoing as a promising disease management strategy in near future. Hence, the present review discusses about the effects of hypoxia on different cellular organelles, mechanisms and their involvement in the progression of different diseases.     

Oxidative Stress in Submerged Cultures of Fungi

ABSTRACT:?

It has been known for many years that oxygen (O₂) may have toxic effects on aerobically growing microorganisms, mainly due to the threat arising from reactive oxygen species (ROS). In submerged culture industrial fermentation processes, maintenance of adequate levels of O₂ (usually measured as dissolved oxygen tension (DOT)) can often be critical to the success of the manufacturing process. In viscous cultures of filamentous cultures, actively respiring, supplying adequate levels of O₂ to the cultures by conventional air sparging is difficult and various strategies have been adopted to improve or enhance O₂ transfer. However, adoption of those strategies to maintain adequate levels of DOT, that is, to avoid O₂ limitation, may expose the fungi to potential oxidative damage caused by enhanced flux through the respiratory system. In the past, there have been numerous studies investigating the effects of DOT on fungal bioprocesses. Generally, in these studies moderately enhanced levels of O₂ supply resulted in improvement in growth, product formation and acceptable morphological changes, while the negative impact of higher levels of DOT on morphology and product synthesis were generally assumed to be a consequence of “oxidative stress.” However, very little research has actually been focused on investigation of this implicit link, and the mechanisms by which such effects might be mediated within industrial fungal processes. To elucidate this neglected topic, this review first surveys the basic knowledge of the chemistry of ROS, defensive systems in fungi and the effects of DOT on fungal growth, metabolism and morphology. The physiological responses of fungal cells to oxidative stress imposed by artificial and endogenous stressors are then critically reviewed. It is clear that fungi have a range of methods available to minimize the negative impacts of elevated ROS, but also that development of the various defensive systems or responses, can itself have profound consequences upon many process-related parameters. It is also clear that many of the practically convenient and widely used experimental methods of simulating oxidative stress, for example, addition of exogenous menadione or hydrogen peroxide, have effects on fungal cultures quite distinct from the effects of elevated levels of O₂, and care must thus be exercised in the interpretation of results from such studies. The review critically evaluates our current understanding of the responses of fungal cultures to elevated O₂ levels, and highlights key areas requiring further research to remedy gaps in knowledge.