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Membrane Androgen Receptor(S) and their Role in Prostate Cancer:A Review 膜雄激素受体及其在前列腺癌中的作用
Pub Date : 2016-12-01 DOI: 10.18519/JER/2016/V20/165440
J. Singh, G. Bhattacharjee
Androgen, a steroid hormone, typically mediates its action by binding to the cytosolic Androgen Receptor (AR), via the classical or genomic pathway. Androgens can also act through a non-classical or non-genomic pathway interacting with receptors present on the plasma membrane of cells. Although the identity of the nuclear AR is well established, the identity of the membrane AR is still not clear. Through independent studies, three proteins have been identified that are present on plasma membranes of prostate cells and can mediate androgen signalling, viz, GPRC6A, AR8 and ZIP9. Although these proteins can mediate androgen signalling, the membrane receptor which is used most frequently and specifically for mediating androgen action in prostate cells is not confirmed. Recent research has shown that the non-genomic androgen signalling plays a key role in progression of prostate cancer (PCa). In this review, the potential of these three proteins for their ability to act as the membrane AR has been analysed. The use of membrane AR as a novel target for the treatment of PCa has also been discussed.
雄激素是一种类固醇激素,通常通过经典或基因组途径与细胞质雄激素受体(AR)结合来调节其作用。雄激素也可以通过非经典或非基因组途径与细胞质膜上的受体相互作用。虽然核AR的身份已经确定,但膜AR的身份仍然不清楚。通过独立研究,已经确定了三种存在于前列腺细胞质膜上并能介导雄激素信号传导的蛋白,即GPRC6A、AR8和ZIP9。虽然这些蛋白可以介导雄激素信号传导,但在前列腺细胞中最常用和专门用于介导雄激素作用的膜受体尚未得到证实。最近的研究表明,非基因组雄激素信号在前列腺癌(PCa)的进展中起着关键作用。在这篇综述中,分析了这三种蛋白作为膜AR的潜力。本文还讨论了膜AR作为治疗PCa的新靶点的应用。
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引用次数: 0
Gestational Exposure to Di(2-ethylhexyl)phthalate Modifies the Expression Pattern of Genes Controlling Thyroid Hormone Biosynthesis in Puberal Rat Progeny 妊娠期暴露于二(2-乙基己基)邻苯二甲酸酯改变青春期大鼠后代甲状腺激素生物合成控制基因的表达模式
Pub Date : 2016-12-01 DOI: 10.18519/JER/2016/V20/165442
S. Elangovan, M. Aruldhas, S. Suganya, P. Rajesh, E. Suthagar, A. Navin, N. Shobana, B. Sankar, R. Ilangovan
Di(2-ethylhexyl) phthalate (DEHP), a plasticizer, is known to disrupt thyroid functions but the underlying molecular mechanism remains obscure. The present study was conducted testing the hypothesis that gestational exposure to DEHP would modify the expression of specific genes controlling biosynthesis and action of thyroid hormones in the male progeny at puberal age. Pregnant rats were administered with DEHP [1, 10 and 100 mg (in olive oil)/Kg b.wt./day] from embryonic day 9 to 21 through oral route. The pups were sacrificed on post-natal day 60. Enzyme Immuno-Assay (EIA) revealed a dose-dependent decrease in serum 3,5,3’ triiodothyronine (T 3 ) and L-thyroxine (T 4 ) titres in DEHP-treated rats. Real-time RT-PCR and western blot analyses of thyroidal genes revealed decreased expression level of sodium/iodide symporter (Nis) and thyroid hormone receptor α (Trα) , whereas the expression of thyroid stimulating hormone receptor (Tshr) , thyroid hormone receptor β (Trβ) and pendrin (Pds) increased. While western blot detection showed decreased expression level of thyroperoxidase (Tpo) , RTPCR data pointed out augmented expression. Western blot detection of transcriptional factors showed decreased expression levels of fork-headbox e1 (Foxe1) and hematopoietically expressed homeobox (Hhex), whereas thyroid transcription factor-1 (Ttf-1) and paired-box domain 8 (Pax8) increased. Our study demonstrates, for the first time, that gestational exposure to DEHP affects the expression of genes controlling thyroid hormone synthesis in puberal rat progeny, and the hypothyroid state in these rats may be linked to decreased expression of Nis, Tpo , Foxe1 and Hhex.
邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种增塑剂,已知会破坏甲状腺功能,但其潜在的分子机制尚不清楚。本研究旨在验证妊娠期暴露于DEHP会改变青春期雄性后代控制甲状腺激素生物合成和作用的特定基因表达的假设。妊娠大鼠分别给予DEHP[1、10和100 mg(橄榄油中)/Kg b.wt。从胚胎第9天至第21天通过口服途径。幼崽在出生后第60天被处死。酶免疫分析(EIA)显示dehp处理大鼠血清3,5,3′三碘甲状腺原氨酸(t3)和l -甲状腺素(t4)滴度呈剂量依赖性降低。Real-time RT-PCR和western blot分析显示,甲状腺基因中碘化钠同转运体(Nis)和甲状腺激素受体α (Trα)的表达水平降低,而促甲状腺激素受体(Tshr)、甲状腺激素受体β (Trβ)和pendrin (Pds)的表达水平升高。western blot检测显示甲状腺过氧化物酶(thyroperoxidase, Tpo)表达水平下降,而RTPCR数据显示表达增强。Western blot检测转录因子显示Foxe1和造血同源盒(Hhex)表达水平降低,而甲状腺转录因子-1 (Ttf-1)和配对盒结构域8 (Pax8)表达水平升高。我们的研究首次证明,妊娠期暴露于DEHP会影响青春期大鼠后代控制甲状腺激素合成的基因的表达,这些大鼠的甲状腺功能低下状态可能与Nis、Tpo、Foxe1和Hhex的表达减少有关。
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引用次数: 0
Seasonal Changes in the Secretory Activity of Seminal Vesicles of the Indian Fruit Bat Rousettus leschenaulti (Desmarest 1820) 印度果蝠精囊分泌活性的季节变化(Desmarest 1820)
Pub Date : 2016-11-03 DOI: 10.18519/jer/2015/v19/131676
A. Nerkar, M. P. Gujar, S. Bande, M. M. Gadegone
The epithelium of the seminal vesicles of Rousettus leschenaultia shows cyclical pattern in the secretory activity during the reproductive cycle. During the sexually quiescent phase, the seminal vesicles are regressed; the cytoplasm of the epithelial cells contains coarse secretory granules and the lumina of the tubules are empty. The secretion is in the form of secretory blebs in this species of bat. The formation of secretory blebs from the columnar epithelial cells is initiated during the recrudescent phase and is at its peak during the active breeding phase. These secretory blebs are discharged into the lumen of the tubules. Lumina of the tubules are filled with secretory blebs during the recrudescent and active breeding phases. Later on these blebs disintegrate and dissolve to form a homogenous material in the lumen of the tubules. Thus, the mode of secretion in the seminal vesicle of Rousettus is apocrine. The functional significance of the secretion of the seminal vesicles in reproduction of male bat is discussed.
在生殖周期中,精囊上皮的分泌活动呈周期性。在性静止期,精囊退化;上皮细胞的细胞质含有粗分泌颗粒,小管腔空。这种蝙蝠的分泌物以分泌泡的形式存在。柱状上皮细胞分泌泡的形成始于复发期,在繁殖活跃期达到顶峰。这些分泌泡被排出到小管的管腔中。在复发期和繁殖期,小管腔内充满分泌泡。随后,这些气泡分解并溶解,在小管的管腔中形成一种均匀的物质。因此,Rousettus精囊的分泌方式为顶浆分泌。讨论了雄性蝙蝠精囊分泌在生殖中的功能意义。
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引用次数: 1
Thyroid Gland in Regulation of Annual Reproduction and Oxidative Metabolism of a Tropical Bird, Perdicula Asiatica :Role of Melatonin and Environmental Factors 甲状腺在热带鸟类亚洲孔雀鸟年繁殖和氧化代谢中的调节作用:褪黑激素和环境因素的作用
Pub Date : 2016-11-03 DOI: 10.18519/jer/2015/v19/131678
V. Verma, S. Yadav, C. Haldar, R. Tripathi
As a transducer of the environmental factors the pineal gland, together with the metabolically active thyroid gland, plays a major role in control of reproduction during different times of the year, in response to the changing environmental conditions of the tropical zone unlike in the temperate zone. Our avian model P. asiatica is a long day breeder. It is reproductively active during summer and quiescent during winter months. In this study we investigated the role of thyroid gland super-imposed by melatonin in the regulation of the annual male reproduction in this bird. The metabolically active thyroid gland presented a functional parallelism with the testicular activity suggesting that thyroid hormone is essential for reproductive activity and related metabolic energy for avian species. Our data also suggest an inhibitory effect of melatonin on thyroid gland function [weight, thyroxine (T3/ T4) level and thymidine kinase activity, THK] both during active and inactive phases of the reproductive cycle. However, this inhibitory effect was less evident during the active phase. The low level of melatonin during the reproductively active phase might be due to long days of summer which prevented the birds from being hyperthyroidic. Therefore, we suggest that the level of melatonin serves as a physiological check to control the seasonal reproductive activities of gonads and thyroid which synergistically play most important physiological roles in energy metabolism of these seasonally breeding bird P. asiatica .
松果体作为环境因素的传感器,与代谢活跃的甲状腺一起,在一年中的不同时期对生殖的控制起着重要作用,以应对热带地区不同于温带地区不断变化的环境条件。我们的鸟类模型亚洲斑蝶是一个长日繁殖者。它在夏季繁殖活跃,在冬季安静。在本研究中,我们研究了褪黑素叠加甲状腺在雄鸟年繁殖调节中的作用。代谢活跃的甲状腺与睾丸活动具有功能上的相似性,表明甲状腺激素对鸟类的生殖活动和相关代谢能量至关重要。我们的数据还表明,在生殖周期的活跃和不活跃阶段,褪黑激素对甲状腺功能[体重,甲状腺素(T3/ T4)水平和胸苷激酶活性,THK]都有抑制作用。然而,这种抑制作用在活性阶段不太明显。繁殖活跃期褪黑素水平较低可能是由于夏季白昼较长,防止了鸟类的甲状腺功能亢进。因此,我们认为褪黑激素水平可以作为控制季节性繁殖鸟类性腺和甲状腺的生理检查,它们在能量代谢中协同起着最重要的生理作用。
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引用次数: 0
Secretion of Mucins in the Fallopian Tube Epithelium of the Bat Taphozous kachhensis Dobson 粘蛋白在蝙蝠输卵管上皮中的分泌
Pub Date : 2016-11-03 DOI: 10.18519/JER/2015/V19/131675
A. Nerkar, K. R. Apkaje, V. G. Jamgade, M. M. Gadegone
Taphozous kachhensis is one of the largest Indian microchiropteran bats with a prominent gular pouch on the ventral side of the lower jaw. This is a seasonally monoestrous species and breeds once in a year. The Fallopian tube epithelium of T. kachhensis in both the segments, ampullary and isthumic, is lined by two cell types: ciliated and non-ciliated (secretory). The Fallopian tube shows alterations in its muco-subtances during estrus and pregnancy. The ciliated cells elaborate large quantity of glycogen, while non-ciliated cells elaborate high amounts of glycogen and neutral and acid mucins during estrus. Mucins are localized in the cytoplasm as well as cytoplasmic blebs. Glycogen and other muco-substances in non-ciliated cells decrease during pregnancy and the ciliated cells show a small amount of glycogen only. The concentration of muco-substances is highest during estrus, and the cytoplasmic blebs are numerous and prominent and are filled with secretion during this stage.
Taphozous kachhensis是印度最大的小翼手目蝙蝠之一,在下颚的腹侧有一个突出的扁平袋。这是一种季节性的单情物种,一年繁殖一次。kachhensis T.输卵管两节段(壶腹和节段)的输卵管上皮由两种类型的细胞排列:纤毛细胞和非纤毛细胞(分泌)。输卵管在发情期和妊娠期粘膜物质发生变化。在发情期间,纤毛细胞分泌大量的糖原,而非纤毛细胞分泌大量的糖原和中性和酸性粘蛋白。粘蛋白局限于细胞质和细胞质泡中。妊娠期间,非纤毛细胞中的糖原和其他黏液物质减少,纤毛细胞仅显示少量糖原。发情期间黏液物质浓度最高,胞浆泡多而突出,充满分泌物。
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引用次数: 0
Aspects of Male Reproductive Toxic Effects of Quassia amara L.: Histopathological and Ultrastructural Study in Mouse 番槐雄性生殖毒性作用的研究:小鼠组织病理学和超微结构研究
Pub Date : 2016-11-03 DOI: 10.18519/jer/2015/v19/131679
K. Faisal, R. Girija, M. A. Akbarsha
Quassia amara is a Brazilian medicinal plant traditionally used as an herbal remedy for a variety of diseases. Quassin is the major secondary chemical compound in it, which is under investigation as an anti-malarial compound. There are preliminary studies implicating Q. amara in male reproductive toxicity. Hence, this elaborate study was undertaken to find the male reproductive toxic effects of Q. amara and quassin. Methanolic extract of Q. amara bark and quassin were administered to male mice for 35 days. The cauda epididymidal sperm, testis and epididymis were subjected to analysis adopting light and transmission electron microscopy. Sperm counts, motility and viability decreased. The incidence of sperm with abnormal morphologies increased. There was premature loss of germ cells from the seminiferous tubules, which correlated with Sertoli cell pathology. The Leydig cells were vacuolated, suggesting a hypo-androgen status. The epididymis indicated severe histopathological changes, including reflection of a mitogenic/tumorigenic effect of Q. amara . Thus, this study indicates that Q. amara , when applied as a therapeutic, could be severely toxic to male reproductive mechanisms and the principal mechanism of action appears to be through Leydig cells. Quassin, the major secondary metabolite responsible for the therapeutic potential of Q. amara , is also the one causative of the male reproductive toxic effects. Thus, this study substantiates the claim that Q. amara is toxic to male reproductive system.
番石榴是一种巴西药用植物,传统上被用作治疗多种疾病的草药。Quassin是其主要的二级化合物,目前正在研究其作为抗疟疾化合物的作用。有初步的研究表明黑螺旋体与男性生殖毒性有关。因此,本研究进行了详细的研究,以发现雄性生殖毒性作用的阿玛拉和瓜辛。雄性小鼠连续35 d服用苦楝皮甲醇提取物和槲皮素。采用光镜和透射电镜对附睾尾精子、睾丸和附睾进行分析。精子数量、活力和活力下降。形态异常精子的发生率增加。精小管的生殖细胞过早丢失,这与支持细胞病理有关。间质细胞呈空泡状,提示雄激素水平低下。附睾显示出严重的组织病理学改变,包括反映了阿玛拉菌的有丝分裂/致瘤作用。因此,本研究表明,当作为一种治疗药物使用时,黄芪可能对男性生殖机制有严重的毒性,其主要作用机制似乎是通过间质细胞。Quassin是一种主要的次生代谢物,具有治疗潜力,也是男性生殖毒性效应的一个原因。因此,本研究证实了黑曲霉对男性生殖系统有毒的说法。
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引用次数: 2
A Compendium of Nuclear Receptors: The Superfamily of Ligand-Modulated Transcription Factors 核受体简编:配体调节转录因子超家族
Pub Date : 2016-06-30 DOI: 10.18519/JER/2016/V20/149824
A. K. Dash, R. Tyagi
The ‘Nuclear Receptor Super-family’ is a group of ligand-modulated transcription factors with 48 members identified in human genome. Members of this family of receptors are now established to be involved in regulation of a plethora of physiological processes in the paradigms of development, reproduction, metabolism and homeostasis. Also, in the myriads of patho-physiological processes, these receptors have consistently exhibited enormous potential as targets for the treatment of diseases such as cancers, osteoporosis, diabetes, obesity, coronary heart disease, asthma, hypertension, thyroid conditions and multiple other metabolic disorders. In recent times, it is estimated that about 15% of the clinical drugs, used in treatments of different ailments, target nuclear receptors. These receptors include steroid/thyroid hormone receptors and orphan/adopted receptors that function as intra-cellular transcription factors to regulate expression of several hundreds of genes in response to their cognate ligands. Interestingly, nuclear receptors are also being assigned a novel role in serving as ‘epigenetic marks’ for the retention and transmission of cellular ‘transcriptional memory’. These receptors function primarily either as homodimers or heterodimers with Retinoid X Receptor (RXR) or sometimes as monomers. Being ‘drug responsive’ these receptors offer attractive targets for drug discovery since their activities can be favorably modulated by interacting ligands. However, many of the newly discovered members of this family of receptors remain incompletely understood, both in terms of physiological roles and activating ligands. In brief, nuclear receptors represent enormous potential for drug discovery and are continuously being examined to unravel the mysteries underlying their mechanisms of action. It has been well-over three decades since the cloning of steroid/nuclear receptors in the 1980s. Therefore, it’s only appropriate to prepare a comprehensive review that provides a compendium of facts and events from receptor cloning and characterization to establishment of receptor domain structures, physiological functioning and consequences of receptor malfunctioning. This review is expected to serve as a refreshing compendium of nuclear receptors for both, the beginners, as well as experts working in the areas of nuclear receptor biology.
“核受体超家族”是一组配体调节的转录因子,在人类基因组中有48个成员。这一受体家族的成员现在被确定参与了发育、繁殖、代谢和体内平衡等多种生理过程的调节。此外,在无数的病理生理过程中,这些受体一直表现出巨大的潜力,作为治疗癌症、骨质疏松症、糖尿病、肥胖、冠心病、哮喘、高血压、甲状腺疾病和多种其他代谢紊乱等疾病的靶点。近年来,据估计,用于治疗不同疾病的临床药物中约有15%是针对核受体的。这些受体包括类固醇/甲状腺激素受体和孤儿/收养受体,它们作为细胞内转录因子调节数百种基因的表达,以响应其同源配体。有趣的是,核受体也被赋予了一个新的角色,作为细胞“转录记忆”的保留和传递的“表观遗传标记”。这些受体主要与类视黄醇X受体(RXR)作为同二聚体或异二聚体起作用,有时也作为单体起作用。作为“药物反应性”,这些受体为药物发现提供了有吸引力的靶标,因为它们的活性可以通过相互作用的配体进行有利的调节。然而,许多新发现的受体家族成员在生理作用和激活配体方面仍未完全了解。简而言之,核受体代表着巨大的药物发现潜力,并不断被研究以揭示其作用机制的奥秘。自20世纪80年代克隆类固醇/核受体以来,已经有30多年了。因此,只有准备一份全面的综述,提供从受体克隆和表征到受体结构域的建立,生理功能和受体功能障碍的后果的事实和事件的概要。这篇综述有望为核受体生物学的初学者和专家提供一个令人耳目一新的核受体纲要。
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引用次数: 3
Mifepristone (RU486) Induces Polycystic Ovarian Syndrome in Female Wistar Rats with Features Analogous to Humans 米非司酮(RU486)诱导具有类似人类特征的雌性Wistar大鼠多囊卵巢综合征
Pub Date : 2015-06-01 DOI: 10.18311/JER/2015/V19/86061
M. Yakubu, F. J. Olawepo, L. Olayaki, O. Ibrahim
Numerous inducers of polycystic ovarian syndrome (PCOS) at different doses have been proposed in several experimental animals but there is no consensus on an appropriate dose(s) that should ideally reproduce the key biochemical and clinical features of PCOS similar to those of humans. Therefore, this study was aimed at investigating an appropriate dose(s) for the induction of PCOS in female Wistar rats. Twenty-four female albino rats (190.00 ± 13.00 g) with 4-5 days of estrus cyclicity were completely randomized into 4 groups (A - D) of six animals each. Animals in group A (control) were subcutaneously administered 0.2 ml of pure olive oil, while those in groups B, C and D were subcutaneously administered same volume corresponding to 5.0, 7.5 and 10.0 mg of mifepristone in olive oil for 9 days starting from the day of estrus (Day 1). The estrus cycle, serum testosterone (T), estradiol (E), prolactin (Pr), follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), insulin (Is), weight of the animals, fasting blood glucose (FBS) and ovarian morphology were monitored/evaluated/examined. The 5.0 mg of mifepristone extended the estrus stage for four days, increased (p<0.05) the levels of serum E, P, Pr, FSH, T, triacylglycerides (TAG), and total cholesterol (TC) as well as decreased the concentrations of LH and high density lipoprotein-cholesterol (HDL-C). There was no significant difference (p<0.05) in the Is concentration, animal body weights and FBS at day 10 in rats administered 5.0 mg of mifepristone. The 7.5 mg of mifepristone produced irregular estrus cycle, increased Pr, TAG, T, and TC concentrations and FBS whereas it decreased E, P, HDL-C, and LH. The Is, FSH and body weights of the animals were not significantly altered at 7.5 mg of mifepristone. The 10.0 mg of mifepristone produced irregular estrus cycle, increased the levels of E, TAG, Is, LH, T as well as decreased the levels of P and HDL-C. The levels of Pr, FSH, TC, body weights and FBS were not significantly altered at this dose. There was no ovarian follicular growth and atresia in the 5.0 and 7.5 mg mifepristone-treated rats whereas the 10 mg of mifepristone produced these histopathological features. Overall, the study concluded that subcutaneous administration of mifepristone (RU486) induces polycystic ovarian syndrome in rats through deprivation of progesterone with the 10 mg producing majority of the key biochemical and clinical features associated with PCOS in humans. The study, therefore, recommends the subcutaneous administration of mifepristone (RU486) on daily basis for 9 days as a good model for inducing PCOS in animals.
许多不同剂量的多囊卵巢综合征(PCOS)诱导剂已经在一些实验动物中被提出,但对于一个合适的剂量,应该理想地再现PCOS的关键生化和临床特征,与人类相似,没有达成共识。因此,本研究旨在探讨诱导雌性Wistar大鼠PCOS的合适剂量。选取24只雌性白化大鼠(190.00±13.00 g),发情周期4 ~ 5 D,完全随机分为4组(A ~ D),每组6只。A组(对照组)动物皮下注射纯橄榄油0.2 ml, B、C、D组动物皮下注射等量的橄榄油米非非酮5.0、7.5、10.0 mg,从发情当天(第1天)开始,连续9 D。测定发情周期、血清睾酮(T)、雌二醇(E)、催乳素(Pr)、促卵泡激素(FSH)、黄体生成素(LH)、孕酮(P)、胰岛素(Is)、体重、监测/评估/检查空腹血糖(FBS)和卵巢形态。5.0 mg米非司酮使大鼠发情期延长4天,血清E、p、Pr、FSH、T、甘油三酯(TAG)、总胆固醇(TC)水平升高(p<0.05), LH和高密度脂蛋白胆固醇(HDL-C)浓度降低(p<0.05)。给药5.0 mg米非司酮对第10天Is浓度、动物体重和FBS均无显著影响(p<0.05)。7.5 mg米非司酮导致发情周期不规则,Pr、TAG、T和TC浓度升高,FBS升高,而E、P、HDL-C和LH降低。7.5 mg米非司酮对大鼠的胰岛素、卵泡刺激素和体重无显著影响。10.0 mg米非司酮使大鼠发情周期不规则,E、TAG、Is、LH、T水平升高,P、HDL-C水平降低。在此剂量下,Pr、FSH、TC、体重和FBS水平无明显变化。5.0和7.5 mg米非司酮组大鼠没有卵巢卵泡生长和闭锁,而10 mg米非司酮组产生这些组织病理学特征。总的来说,该研究得出结论,皮下给药米非司酮(RU486)通过剥夺孕酮诱导大鼠多囊卵巢综合征,其中10毫克产生与人类多囊卵巢综合征相关的大多数关键生化和临床特征。因此,本研究推荐每日皮下给药米非司酮(RU486) 9天作为诱导PCOS的良好动物模型。
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引用次数: 2
Oxidative Stress Responses of a Freshwater Teleost, Anabas testudineus , to an Endocrine Disruptor, Bisphenol A 淡水硬骨鱼对内分泌干扰物双酚a的氧化应激反应
Pub Date : 2015-06-01 DOI: 10.18519/JER/2015/V19/86045
C. A. Devi, R. Binitha, S. Soorya, B. Amrutha, F. Sunny
Bisphenol-A (BPA), an industrial chemical used to manufacture polycarbonate plastic, is considered as a potent estrogenic endocrine disruptor. A majority of xenobiotics exert their toxic effect by causing generation of reactive oxygen species, leading to oxidative stress. Reports regarding oxidative stress responses to BPA in fish are scanty. From this viewpoint, in the present study, a freshwater fish, Anabas testudineus , was exposed to sub-lethal concentrations of BPA (2.5, 5.0,&7.5 mg/l), for different time periods (7, 15&30 days). Four major enzymes of the fish's antioxidant defense system viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (Se-GPx), and glutathione-S-transferase (GST), and the non-enzymatic antioxidant glutathione (GSH) were chosen as biomarkers to examine the effects of BPA. The activities of SOD, GPx and GSH were elevated to significant levels, while CAT and GST activities were decreased significantly suggesting oxidative stress in BPAexposed fish. Reactive oxygen species are known to cause DNA fragmentation. Hence, DNA fragmentation assay was also done. The severity of DNA fragmentation in fish exposed to 7.5 mg/L BPA (30days) was remarkably increased (p<0.05 vs control) and this was revealed in gel electrophoresis analysis also. The results clearly show that BPA is a pollutant with oxidative potential, also with a potential for DNA fragmentation. The potential risks of this compound to nature and human populations are significant since the production of BPA related compounds is increasing dramatically each year.
双酚a (BPA)是一种用于制造聚碳酸酯塑料的工业化学品,被认为是一种强效的雌激素内分泌干扰物。大多数外源药物通过产生活性氧来发挥其毒性作用,从而导致氧化应激。关于鱼对BPA的氧化应激反应的报道很少。从这个角度来看,在本研究中,一种淡水鱼testudineus暴露在亚致死浓度的BPA(2.5、5.0和7.5 mg/l)中,时间不同(7天、15天和30天)。选择鱼类抗氧化防御系统的四种主要酶,过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(Se-GPx)和谷胱甘肽- s -转移酶(GST),以及非酶抗氧化剂谷胱甘肽(GSH)作为生物标志物,研究BPA的作用。SOD、GPx和GSH活性显著升高,CAT和GST活性显著降低,提示bpa暴露后鱼体出现氧化应激。众所周知,活性氧会导致DNA断裂。因此,还进行了DNA片段分析。暴露于7.5 mg/L BPA (30d)的鱼的DNA断裂程度显著增加(p<0.05),凝胶电泳分析也显示了这一点。结果清楚地表明,BPA是一种具有氧化潜力的污染物,也有可能导致DNA断裂。这种化合物对自然和人类的潜在风险是巨大的,因为BPA相关化合物的产量每年都在急剧增加。
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引用次数: 1
Cross Talk between Protein Kinase A and Androgen Signaling Pathway 蛋白激酶A与雄激素信号通路的串扰
Pub Date : 2015-06-01 DOI: 10.18519/JER/2015/V19/86041
Manisha Dagar, G. Bhattacharjee
Protein kinases are enzymes that add phosphate group to proteins to modify their function. These proteins regulate signal transduction pathways, essential for many biological processes such as cell cycle, cell signaling, protein and enzyme regulation, etc. There are 518 protein kinases, divided in to 7 main families. Protein kinase A (PKA) is a member of AGC family of protein kinases. It is activated by activation of G protein-coupled receptors (GPCR) and plays an important role in many cellular pathways including androgen signaling. Steroid hormones such as androgens primarily function through a genomic pathway, binding to cytosolic androgen receptors (AR) and initiating changes in transcription of target genes. Androgens also functions through a non-genomic pathway which is rapid and mediated by membrane receptors. It manifests its effects by activation of cellular signal transduction pathways such as PKA, Protein kinase C, and mitogen activated kinase, and does not involve transcription. In this review, we have analyzed the interaction between androgen signaling pathways and PKA, and have highlighted how each of these pathways complements and strengthens the function of the other. PKA plays an important role in complete activation of nuclear AR and in turn PKA can be activated by androgens. The complex interaction between the two pathways plays a critical role in development and progression of prostate cancer (PCa). Though the exact role of each pathway is not completely understood yet simultaneous inhibition of both pathways could prove to be beneficial for PCa patients.
蛋白激酶是在蛋白质上添加磷酸基团以改变其功能的酶。这些蛋白调节信号转导通路,在细胞周期、细胞信号传导、蛋白质和酶调节等许多生物过程中起重要作用。有518种蛋白激酶,分为7个主要家族。蛋白激酶A (PKA)是AGC蛋白激酶家族的一员。它通过G蛋白偶联受体(GPCR)的激活而激活,在包括雄激素信号在内的许多细胞通路中起重要作用。类固醇激素如雄激素主要通过基因组途径发挥作用,与细胞质雄激素受体(AR)结合并启动靶基因转录的变化。雄激素也通过非基因组途径发挥作用,该途径是由膜受体介导的快速途径。它通过激活细胞信号转导通路如PKA、蛋白激酶C和丝裂原活化激酶来表现其作用,不涉及转录。在这篇综述中,我们分析了雄激素信号通路和PKA之间的相互作用,并强调了这些通路如何相互补充和增强功能。PKA在核AR的完全激活中起重要作用,而PKA又可被雄激素激活。这两种通路之间复杂的相互作用在前列腺癌(PCa)的发生和发展中起着关键作用。虽然每个途径的确切作用还不完全清楚,但同时抑制这两个途径可能对PCa患者有益。
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引用次数: 2
期刊
Journal of Endocrinology and Reproduction
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