arsenic toxicity

  • 文章类型: Journal Article
    氧化苯胺(PAO)是已知的环境污染物,皮肤角质形成细胞受到最严重的影响。据报道,黄芩苷(BCN)具有抗氧化和抗炎作用,但其对PAO毒性的保护作用尚不清楚。这项研究旨在探索黄芩苷是否可以逆转人表皮角质形成细胞受到PAO暴露的毒性和潜在机制。暴露于慢性砷的公开HaCaT细胞转录组数据集的计算机模拟分析显示了几个基因的显著差异表达,包括与DNA复制相关的基因。稍后,我们进行了体外实验,其中HaCaT细胞在BCN(10-50μM)存在下暴露于PAO(500nM)。单独治疗PAO诱导JNK,p38和caspase-3激活,参与细胞凋亡诱导,而AKT的活性被显著抑制,参与抑制细胞凋亡。PAO抑制SIRT3表达并诱导细胞内活性氧(ROS),导致细胞活力和细胞凋亡的显著降低。然而,BCN处理恢复了PAO诱导的SIRT3和AKT表达的抑制,减少细胞内ROS的产生,并显着抑制caspase-3的激活和凋亡诱导。然而,烟酰胺预处理后BCN的保护作用显着减弱,SIRT3的抑制剂。这些发现表明,BCN通过恢复SIRT3活性并重新激活下游AKT途径来抑制过度的细胞内ROS产生,从而防止PAO诱导的细胞死亡。在这项研究中,我们首先证明了BCN是一种有效的预防PAO引起的皮肤细胞毒性的药物,这些发现需要通过体内和临床研究来证实。
    Phenylarsine oxide (PAO) is a known environmental pollutant and skin keratinocytes are most seriously affected. Baicalin (BCN) was reported to have antioxidant and anti-inflammatory effects, but its protective effect against PAO toxicity is unknown. This study aimed at exploring whether baicalin can reverse the toxicity of human epidermal keratinocytes that are subjected to PAO exposure and underlying mechanisms. In silico analysis from a publicly accessible HaCaT cell transcriptome dataset exposed to chronic Arsenic showed significant differential expression of several genes, including the genes related to DNA replication. Later, we performed in vitro experiments, in which HaCaT cells were exposed to PAO (500 nM) in the existence of BCN (10-50 µM). Treatment of PAO alone induces the JNK, p38 and caspase-3 activation, which were engaged in the apoptosis induction, while the activity of AKT was significantly inhibited, which was engaged in the suppression of apoptosis. PAO suppressed SIRT3 expression and induced intracellular reactive oxygen species (ROS), causing a marked reduce in cell viability and apoptosis. However, BCN treatment restored the PAO-induced suppression of SIRT3 and AKT expression, reduced intracellular ROS generation, and markedly suppressed both caspase-3 activation and apoptosis induction. However, the protective effect of BCN was significantly attenuated after pretreatment with nicotinamide, an inhibitor of SIRT3. These findings indicate that BCN protects against cell death induced by PAO via inhibiting excessive intracellular ROS generation via restoring SIRT3 activity and reactivating downstream AKT pathway. In this study, we firstly shown that BCN is an efficient drug to prevent PAO-induced skin cytotoxicity, and these findings need to be confirmed by in vivo and clinical investigations.
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  • 文章类型: Journal Article
    结论:在定植植物中,Serendipita诱导的代谢重编程补充了磷管理,以提高其对砷胁迫的耐受性。恢复人类对环境的破坏与制定不仅在经济上合理,而且具有自我更新和生态意识的策略密不可分。重金属(HM)膳食摄入的困境,特别是砷(As),面对人类和动物,有必要开发这种技术并种植健康和丰富的作物。植物和“菌根”之间非凡的共生联盟已经进化了数千年,有利于生长/产量方面,并赋予非生物/生物胁迫耐受性。Serendipitaindica复杂的相互依存关系(S.印度)和水稻植物据报道减少了砷的积累,强调微生物学家的兴趣,农业学家,和生态毒理学科学家介绍了土壤-AMF-水稻系统中砷的修复机制。营养管理,特别是磷(P),还因通过阻止根际阳离子竞争而吸收As分子而减轻As的植物毒性而受到赞誉。考虑到水稻植物最大限度地减少As获取的合理成功前景,这篇综述集中在生理上,新陈代谢,和S.in共生潜在的转录改变,通过收集案例研究并提出成功的范例,恢复As压力与P的营养管理。编织一卷文学作品,我们评估了As的化学形式和相关的运输途径,讨论As-P-水稻的相互作用以及真菌在减轻As毒性中的意义,主要是菌根的作用,以及对S.in对植物的多方面影响的调查。提出了在稻田中同时施用S.in的潜在策略。其次是未来的研究方向,以扩大理论理解并鼓励基于领域的实施。
    CONCLUSIONS: Serendipita indica induced metabolic reprogramming in colonized plants complements phosphorus-management in improving their tolerance to arsenic stress on multifaceted biological fronts. Restoration of the anthropic damage done to our environment is inextricably linked to devising strategies that are not only economically sound but are self-renewing and ecologically conscious. The dilemma of heavy metal (HM) dietary ingestion, especially arsenic (As), faced by humans and animals alike, necessitates the exploitation of such technologies and the cultivation of healthy and abundant crops. The remarkable symbiotic alliance between plants and \'mycorrhizas\' has evolved across eons, benefiting growth/yield aspects as well as imparting abiotic/biotic stress tolerance. The intricate interdependence of Serendipita indica (S. indica) and rice plant reportedly reduce As accumulation, accentuating the interest of microbiologists, agriculturists, and ecotoxicological scientists apropos of the remediation mechanisms of As in the soil-AMF-rice system. Nutrient management, particularly of phosphorus (P), is also praised for mitigating As phytotoxicity by deterring the uptake of As molecules due to the rhizospheric cationic competition. Taking into consideration the reasonable prospects of success in minimizing As acquisition by rice plants, this review focuses on the physiological, metabolic, and transcriptional alterations underlying S. indica symbiosis, recuperation of As stress together with nutritional management of P by gathering case studies and presenting successful paradigms. Weaving together a volume of literature, we assess the chemical forms of As and related transport pathways, discuss As-P-rice interaction and the significance of fungi in As toxicity mitigation, predominantly the role of mycorrhiza, as well as survey of the multifaceted impacts of S. indica on plants. A potential strategy for simultaneous S. indica + P administration in paddy fields is proposed, followed by future research orientation to expand theoretic comprehension and encourage field-based implementation.
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  • 文章类型: Journal Article
    砷(As)是一种广泛存在的准金属,具有众所周知的毒性。迄今为止,许多研究都集中在个体水平的毒性(例如,生长和繁殖)对土壤中典型的无脊椎动物跳尾鱼的影响,然而,分子水平的毒性和机制知之甚少。这里,整合的转录组学和代谢组学方法用于揭示暴露于10和60mgkg-1的As(V)的念珠菌的反应,在这些反应中,个体水平的终点受到影响.转录组学在低浓度和高浓度组中鉴定了5349和4020个差异表达基因(DEG),分别,大多数DEG被下调。富集分析表明,低浓度和高浓度的As(V)显着抑制染色质/染色体相关的生物学过程(染色质/染色体组织,核小体组装和组织,等。)在春尾。在高浓度处理下,角质层的结构成分,几丁质代谢过程和肽酶活性(丝氨酸型肽酶活性,内肽酶活性,等。)被抑制或扰乱。此外,显著诱导凋亡途径。代谢组学分析确定了暴露于高浓度As的春尾中271种差异变化的代谢物(DCM)。类固醇激素生物合成是受影响最显著的途径。与几丁质代谢相关的几种DCM可以进一步支持上述转录组结果。这些发现进一步将As毒性机制的知识扩展到土壤动物,并为环境风险评估提供了重要信息。
    Arsenic (As) is a widespread metalloid with well-known toxicity. To date, numerous studies have focused on individual level toxicity (e.g., growth and reproduction) of As to typical invertebrate springtails in soils, however, the molecular level toxicity and mechanism was poorly understood. Here, an integrated transcriptomics and metabolomics approach was used to reveal responses of Folsomia candida exposed to As(V) of 10 and 60 mg kg-1 at which the individual level endpoints were influenced. Transcriptomics identified 5349 and 4020 differentially expressed genes (DEGs) in low and high concentration groups, respectively, and the most DEGs were down-regulated. Enrichment analysis showed that low and high concentrations of As(V) significantly inhibited chromatin/chromosome-related biological processes (chromatin/chromosome organization, nucleosome assembly and organization, etc.) in springtails. At high concentration treatment, structural constituent of cuticle, chitin metabolic process and peptidase activity (serine-type peptidase activity, endopeptidase activity, etc.) were inhibited or disturbed. Moreover, the apoptosis pathway was significantly induced. Metabolomics analysis identified 271 differential changed metabolites (DCMs) in springtails exposed to high concentration of As. Steroid hormone biosynthesis was the most significantly affected pathway. Several DCMs that related to chitin metabolism could further support above transcriptomic results. These findings further extended the knowledge of As toxic mechanisms to soil fauna and offer important information for the environmental risk assessment.
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  • 文章类型: Journal Article
    在大自然中,砷主要以无机化合物的形式存在。无机砷化合物有多种用途,目前用于制造农药,防腐剂,制药,等。虽然无机砷被广泛使用,砷污染在全球范围内日益增加。饮用水和土壤砷污染造成的公共危害日益明显。流行病学和实验研究已将无机砷暴露与许多疾病的发展联系起来,包括认知障碍,心血管衰竭,癌症,等。已经提出了几种机制来解释砷引起的影响,如氧化损伤,DNA甲基化,和蛋白质错误折叠。了解砷的毒理学和潜在的分子机制可以帮助减轻其有害影响。因此,本文综述了无机砷对动物的多器官毒性,重点研究了砷引起的动物疾病的各种毒性机制。此外,为了从不同途径降低砷污染的危害,我们总结了几种对砷中毒有治疗作用的药物。
    In nature, arsenic is mostly found in the form of inorganic compounds. Inorganic arsenic compounds have a variety of uses and are currently used in the manufacture of pesticides, preservatives, pharmaceuticals, etc. While inorganic arsenic is widely used, arsenic pollution is increasing worldwide. Public hazards caused by arsenic contamination of drinking water and soil are becoming increasingly evident. Epidemiological and experimental studies have linked inorganic arsenic exposure to the development of many diseases, including cognitive impairment, cardiovascular failure, cancer, etc. Several mechanisms have been proposed to explain the effects caused by arsenic, such as oxidative damage, DNA methylation, and protein misfolding. Understanding the toxicology and potential molecular mechanisms of arsenic can help mitigate its harmful effects. Therefore, this paper reviews the multiple organ toxicity of inorganic arsenic in animals, focusing on the various toxicity mechanisms of arsenic-induced diseases in animals. In addition, we have summarized several drugs that can have therapeutic effects on arsenic poisoning in pursuit of reducing the harm of arsenic contamination from different pathways.
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  • 文章类型: Journal Article
    在生态可持续获取粮食安全的背景下,砷(As)是一种威慑因素,很容易通过植物吸收渗入我们的食物链。因此,设计气候智能型战略对于最大限度地减少强加的风险变得迫在眉睫。相应地,Serendipitaindica(S.印度)以其共生后缓解压力和促进植物生长的潜力而闻名。磷(P)的管理因根际竞争性阳离子交换而抑制As分子的吸收而减轻了植物中砷的毒性。本研究旨在研究S.in和P在使用两种水稻基因型对抗As毒性中的串联作用,即,国道-6(GD-6;As敏感基因型)和中哲优1(ZZY-1;As耐受基因型)。真菌定植成功后,单独使用砷(10μML-1)和磷(50μML-1)处理。结果表明,S.in和P联合治疗的恢复效果确实比单独治疗要深远得多;但是,与GD-6相比,ZZY-1利用了大多数有益影响。观察到抗氧化酶活性的明显基因型差异,在in虫定植的ZZY-1植物中诱导的稍高,有或没有额外的P,与GD-6相比。根和芽的超微结构图像以叶绿体的形式表现出As的破坏-,细胞核和细胞壁损伤,空泡面积扩大,在两种基因型中,主要是通过联合处理印度链球菌和P而变得更加成熟。在跨基因型的几乎所有处理中,PHTs家族转运蛋白的基因表达在不同水平受到调控。最后,这项研究的结果验证了S.in和额外的P在缓解As压力方面的有希望的作用,尽管证实了相关利益利用的程度高度依赖于基因型。Verily,释放对自然友好的解决方案的潜力将弥补已经对我们的环境造成的人为损害。
    In the context of eco-sustainable acquisition of food security, arsenic (As) acts as a deterring factor, which easily infiltrates our food chain via plant uptake. Therefore, devising climate-smart strategies becomes exigent for minimizing the imposed risks. Pertinently, Serendipita indica (S. indica) is well reputed for its post-symbiotic stress alleviatory and phyto-promotive potential. Management of phosphorus (P) is acclaimed for mitigating arsenic toxicity in plants by inhibiting the uptake of As molecules due to the competitive cationic exchange in the rhizosphere. The current study was designed to investigate the tandem effects of S. indica and P in combating As toxicity employing two rice genotypes, i.e., Guodao-6 (GD-6; As-sensitive genotype) and Zhongzhe You-1 (ZZY-1; As-tolerant genotype). After successful fungal colonization, alone and combined arsenic (10  μ M L-1) and phosphorus (50  μ M L-1) treatments were applied. Results displayed that the recuperating effects of combined S. indica and P treatment were indeed much profound than their alone treatments; however, most of the beneficial influences were harnessed by ZZY-1 in comparison with GD-6. Distinct genotypic differences were observed for antioxidant enzyme activities, which were induced slightly higher in S. indica-colonized ZZY-1 plants, with or without additional P, as compared to GD-6. Ultrastructure images of root and shoot exhibited ravages of As in the form of chloroplasts-, nuclei-and cell wall-damage with enlarged vacuole area, mellowed mostly by the combined treatment of S. indica and P in both genotypes. Gene expression of PHTs family transporters was regulated at different levels in almost all treatments across genotypes. Conclusively, the results of this study validated the promising role of S. indica and additional P in mitigating As stress, albeit corroborated that the extent of relevant benefit exploitation is highly genotype-dependent. Verily, unlocking the potential of nature-friendly solutions will mend the anthropogenic damage already been done to our environment.
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  • 文章类型: Journal Article
    淡水中的砷污染对水生生物构成严重威胁。然而,水中溶解的有机物(DOM)可以通过抑制或促进砷的生物积累来调节砷的环境毒性。在这项研究中,我们调查了毒性,生物蓄积性,和生物转化无机砷(亚砷酸盐AsIII和砷酸盐AsV)结合两种类型的DOM,即,腐殖酸(HA)和富里酸(FA),在莱茵衣藻和大黄藻中。莱茵hardtii有细胞壁,不能生物积累络合砷,而O.danica没有细胞壁。没有DOM,AsV对莱茵衣原体的毒性比AsIII更大,ASV对O.danica的毒性比AsIII小。HA和FA的添加降低了AsV和AsIII的毒性;HA的较大分子量(Mw)有助于在更大程度上降低毒性。减少砷的积累,同时促进莱茵酵母的生物转化能力,有一个细胞壁。然而,HA和FA的添加增加了AsV和AsIII的毒性和砷的积累,同时相对增强了O.danica的生物转化能力,它没有细胞壁。偶联毒性,生物蓄积性,和生物转化,DOM(HA和FA)通过减少/增加砷的积累和增强生物转化来改变淡水藻类对AsV和AsIII的毒性。总的来说,我们的研究考虑了浮游植物中无机砷和DOM的联合毒性,帮助估计砷在水环境中的潜在环境风险。
    Arsenic pollution in freshwater poses a serious threat to aquatic organisms. However, dissolved organic matter (DOM) in water can modulate arsenic environmental toxicity by either suppressing or promoting its bioaccumulation. In this study, we investigated the toxicity, bioaccumulation, and biotransformation of inorganic arsenic (arsenite AsIII and arsenate AsV) combined with two types of DOM, i.e., humic acid (HA) and fulvic acid (FA), in the algae Chlamydomonas reinhardtii and Ochromonas danica. C. reinhardtii has a cell wall and cannot bioaccumulate arsenic complexation, whereas O. danica has no cell wall. Without DOM, AsV was more toxic than AsIII for C. reinhardtii, and AsV was less toxic than AsIII for O. danica. HA and FA addition reduced AsV and AsIII toxicities; the larger molecular weight (Mw) of HA contributed to the reduction in toxicity to an even greater extent, and reduced arsenic accumulation while promoting the biotransformation ability of C. reinhardtii, which has a cell wall. However, HA and FA addition increased AsV and AsIII toxicities and arsenic accumulation while relatively enhancing the biotransformation ability of O. danica, which has no cell wall. Coupling toxicity, bioaccumulation, and biotransformation, DOM (HA and FA) contributed to the altered toxicity of freshwater algae to AsV and AsIII through reduced/increased arsenic accumulation and enhanced biotransformation. Overall, our study considered the combined toxicity of inorganic arsenic and DOM in phytoplankton, helping estimate the potential environmental risk of arsenic in aqueous environments.
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  • 文章类型: Journal Article
    环境中的类金属污染是对我们的生态系统构成威胁的严重问题之一。非金属浓度过量(包括锑,砷,硼,硒等)在土壤中导致它们在植物组织中的过度积累,最终导致植物毒性和生物放大。所以,找到一些生态友好的方法来应对上述准金属对植物系统的负面影响非常重要。油菜素类固醇(BRs)属于植物甾体激素家族,并被认为是对抗类金属植物毒性的生态方法之一。这种植物激素通过调节各种关键的生物过程如细胞信号传导来调节类金属存在下的植物生物学,初级和次级代谢,生物分子串扰和氧化还原稳态。本综述解释了在存在类金属的情况下BR调节植物反应的深入机制,并提供了一些生物技术方面的方法来生态友好地管理类金属污染。
    Metalloid contamination in the environment is one of the serious concerns posing threat to our ecosystems. Excess of metalloid concentrations (including antimony, arsenic, boron, selenium etc.) in soil results in their over accumulation in plant tissues, which ultimately causes phytotoxicity and their bio-magnification. So, it is very important to find some ecofriendly approaches to counter negative impacts of above mentioned metalloids on plant system. Brassinosteroids (BRs) belong to family of plant steroidal hormones, and are considered as one of the ecofriendly way to counter metalloid phytotoxicity. This phytohormone regulates the plant biology in presence of metalloids by modulating various key biological processes like cell signaling, primary and secondary metabolism, bio-molecule crosstalk and redox homeostasis. The present review explains the in-depth mechanisms of BR regulated plant responses in presence of metalloids, and provides some biotechnological aspects towards ecofriendly management of metalloid contamination.
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  • 文章类型: Journal Article
    大米仍然是快速增长的世界人口的主要主食来源。然而,淹水水稻表层土壤中经常发生的致癌砷(As)矿物质对全球水稻生产和消费者构成了巨大威胁。尽管在过去的二十年里,水稻中的污染已经得到了很好的认识,尚未确定合适的水稻种质可用于适应性育种计划。因此,本研究根据各种性状鉴定了水稻种质的As耐受性和排除性,并研究了不同生长阶段有利性状的相互联系。系统地评估了53种不同基因型的As耐受性和积累。进行发芽筛选测定以鉴定个体种质在变化的As胁迫下发芽的能力。在不同的As胁迫下在水培中进行苗期筛选,以鉴定耐受性和排除性基因型,并进行了田间试验,以鉴定在谷物中积累较少As的基因型。不考虑水稻基因型,随着处理中As的增加,植物健康状况显着下降。然而,发芽中的基因型依赖性变异,容忍度,在基因型之间观察到As积累。某些基因型(WTR1-BRRIdhan69,NPT-IR68552-55-3-2,OM997和GSRIR1-5-Y4-S1-Y1)通过在芽系统中排除As而表现出高耐受性。谷物中的砷含量范围从中国的黄华詹中的0.12mgkg-1到巴西的IRAT109中的0.48mgkg-1。本研究为水稻基因型在不同生长阶段的不同As胁迫下的表现提供了新的见解,可进一步用于正在进行的育种计划,以开发As污染环境中的As排除水稻品种。
    Rice remains a major staple food source for the rapidly growing world population. However, regular occurrences of carcinogenic arsenic (As) minerals in waterlogged paddy topsoil pose a great threat to rice production and consumers across the globe. Although As contamination in rice has been well recognized over the past two decades, no suitable rice germplasm had been identified to exploit in adaptive breeding programs. Therefore, this current study identified suitable rice germplasm for As tolerance and exclusion based on a variety of traits and investigated the interlinkages of favorable traits during different growth stages. Fifty-three different genotypes were systematically evaluated for As tolerance and accumulation. A germination screening assay was carried out to identify the ability of individual germplasm to germinate under varying As stress. Seedling-stage screening was conducted in hydroponics under varying As stress to identify tolerant and excluder genotypes, and a field experiment was carried out to identify genotypes accumulating less As in grain. Irrespective of the rice genotypes, plant health declined significantly with increasing As in the treatment. However, genotype-dependent variation in germination, tolerance, and As accumulation was observed among the genotypes. Some genotypes (WTR1-BRRI dhan69, NPT-IR68552-55-3-2, OM997, and GSR IR1-5-Y4-S1-Y1) showed high tolerance by excluding As in the shoot system. Arsenic content in grain ranged from 0.12 mg kg-1 in Huang-Hua-Zhan (indica) from China to 0.48 mg kg-1 in IRAT 109 (japonica) from Brazil. This current study provides novel insights into the performance of rice genotypes under varying As stress during different growth stages for further use in ongoing breeding programs for the development of As-excluding rice varieties for As-polluted environments.
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  • 文章类型: Journal Article
    在世界不同地区,砷(As)污染的土壤对植物生长及其生理过程构成严重威胁。有机改良剂是一种经济有效且环保的方法,可在受污染土壤的胁迫条件下改善植物生长。在被污染的酸性多溶胶中,进行了一项温室试验,以研究花生秸秆生物炭(PSB)和油菜秸秆生物炭(CSB)对大豆矿物质营养的保护作用。抗氧化酶,和生理生长参数。目前的研究使用了18种不同水平的As((1)0mgkg-1,(2)30mgkg-1,(3)60mgkg-1)和生物炭(PSB和CSB)(0%,1%,和2%)。结果表明,在高度风化的酸性土壤中,在As胁迫下添加生物炭增加了大豆的生长属性和防御机制。PSB以剂量依赖性方式比CSB更有效。在污染土壤中施用2%PSB导致大豆高度显着增加(58%),生物量生产(根(44%)和茎长(52%)),叶绿素含量(92%),大豆功能叶(62%),总可溶性糖(TSS)(71%)和碱性阳离子(Ca2+,Mg2+,K+,Na+)。然而,生物炭应用减少脯氨酸,MDA,H2O2和O2+64%,82%,49%,分别为45%。此外,生物炭的应用增加了大豆对磷和砷的吸收,PSB应用表现出比CSB应用更大的增长。因此,作物秸秆衍生的生物炭可以减少As引起的大豆植物损害,并在As污染的酸性多重质土壤中发挥保护作用。
    In different regions of the world, arsenic (As) contaminated soils poses a serious threat to plant growth and its physiological processes. Organic amendments are a cost-effective and environmentally friendly way to improve plant growth under stress conditions in contaminated soils. In As polluted acidic ultisol, a greenhouse trial was conducted to investigate the protective effects of peanut straw biochar (PSB) and canola straw biochar (CSB) on soybean mineral nutrition, antioxidant enzymes, and physiological growth parameters. The current study used eighteen treatments with different levels of As ((1) 0 mg kg-1, (2) 30 mg kg-1, (3) 60 mg kg-1) and biochar (PSB and CSB) (0%, 1%, and 2%). The result suggests that biochar addition under As stress in highly weathered acidic ultisol soil increased soybean growth attributes and defense mechanisms. The PSB was more effective than the CSB in a dose-dependent manner. The application of 2% PSB in polluted soil resulted in significant increases in soybean height (58%), biomass production (root (44%) and shoot length (52%)), chlorophyll contents (92%), soybean functional leaves (62%), total soluble sugars (TSS) (71%) and base cations (Ca2+, Mg2+, K+, Na+). However, biochar application decreased proline, MDA, H2O2, and O2- by 64%, 82%, 49%, and 45% respectively. Furthermore, biochar application increased (Phosphate) P and As uptake in soybean, with PSB application exhibiting a greater increase than CSB application. As a result, crop straw-derived biochar can reduce As-induced soybean plant damage and insert a protective effect in As-contaminated acidic ultisol soils.
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  • 文章类型: Journal Article
    砷(As),一种广泛的环境污染物,会导致严重的男性生殖损伤;然而,潜在机制尚不清楚.多组学分析,包括转录组,蛋白质组,和磷酸蛋白质组可以促进我们对As诱导的男性生殖毒性的理解。这里,通过腹腔注射NaAsO2(8mg/kg体重)建立小鼠生殖系统损伤模型,通过减少生殖细胞验证,精子运动性,和垃圾大小。随后对小鼠进行的多组学分析显示,As暴露通过降低蛋白质HK1和GAPDHS的表达来抑制ATP的产生,以及PDH和SDH的酶活性。线粒体活性的抑制和HDAC2和MTA3的增加失调了组蛋白和全局蛋白的赖氨酸乙酰化水平。具体来说,下调的组蛋白H4K5ac和H4K12ac和上调的组蛋白H3K9ac扰乱了TP1的分布以干扰精子发生。此外,可以减少COL1A1,RAB13和LSR的表达以破坏生精小管之间的连接,其中,抑制RAB13增加PKA依赖性磷酸化。我们的研究表明,As通过减少能量产生导致男性生殖毒性,改变组蛋白乙酰化,并损害细胞连接。我们的发现为进一步研究As生殖毒性提供了基础数据。
    Arsenic (As), a widespread environmental contaminant, can induce serious male reproductive injury; however, the underlying mechanisms remain unclear. Multi-omics analyses, including transcriptome, proteome, and phosphoproteome could promote our understanding of As-induced male reproductive toxicity. Here, we established the reproductive injured mice model by intraperitoneal injection of NaAsO2 (8 mg/kg body weight), which was validated by reduced reproductive cells, sperm motility, and litter size. The followed multi-omics analyses of mice revealed that As exposure inhibited ATP production by decreasing the expression of proteins HK1, and GAPDHS, and the enzymatic activities of PDH and SDH. The inhibition of mitochondrial activity and increase in HDAC2 and MTA3 dysregulated the lysine acetylation levels of histone and global proteins. Specifically, the downregulated histones H4K5ac and H4K12ac and upregulated histone H3K9ac disordered the distribution of TP1 to interfere with spermatogenesis. Moreover, As could reduce the expression of COL1A1, RAB13, and LSR to disrupt the junctions between seminiferous tubules, and thereinto, the inhibition of RAB13 increased PKA-dependent phosphorylation. Our study reveals that As causes male reproductive toxicity through decreasing energy production, altering histone acetylation, and impairing cell junctions. Our findings provide basic data for further studies on As reproductive toxicity.
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