长波紫外线辐射对脊椎动物的影响

臭氧层空洞的加剧使紫外辐射不断加强,造成的环境污染已经成为广为关注的问题,但大多数都集中在中波紫外线(UVB)的生物学作用及其与两栖动物衰减关系的研究,有关长波紫外线(UVA)对生物体损伤作用的研究却甚少。本文综述了近年来UVA对脊椎动物损伤的研究概况,从细胞结构、酶活性、遗传物质、膜结构以及免疫系统等方面阐述了UVA的损伤机理,并对低剂量辐射诱导兴奋效应对紫外损伤的保护作用进行了简要概述。最后分析和总结了关于UVA损伤研究所存在的问题及两栖动物作为实验用动物模型在研究紫外线损伤中的作用。     

TNF-α信号传导通路的分子机理

肿瘤坏死因子α（tumor necrosis factor-alpha,TNF-α）是一种具有多效生物学效应的细胞因子.TNF的生物学效应都是通过细胞表面的2种TNF受体（TNFR）引发,其信号传导通路主要包括caspase家族介导的细胞凋亡、衔接蛋白TRAF介导的转录因子NF-κB和JNK蛋白激酶的活化.TNFR1和TNFR2的生物学功能不是独立的,许多生物学活性由二者共同完成.3条信号传导通路之间及各通路内部含有各种调节机制,使TNF的各种生物学功能协调发挥出来.本文评述了3条信号传导通路最新进展、关键激酶的研究状况及其在整个信号网络中的作用机理,如IKK的激活以及重要的信号转导分子RIP、TRAF2、TRUSS的结构、相互作用的方式等     

Wnt信号膜质转导的机制

Wnt信号通路是一条高度保守的信号转导通路,在生物体多个发育过程以及一系列疾病发生中发挥重要作用。Wnt信号通路重要的生物学功能和复杂的信号转导调控网络引起了人们广泛和持续的研究兴趣。介绍了经典Wnt信号通路信号转导的分子框架,结合自身实验室新的研究发现,重点阐述Wnt信号由细胞膜上向细胞质内转导的机制。     

上皮细胞转分化的信号转导研究进展及其在肾小管的研究现状

上皮细胞在特定生理和病理情况下向间充质细胞转分化的现象是肿瘤及慢性炎症性疾病中的重要细胞生物学现象。近年来研究发现 ,细胞内信号转导途径中的MAPK通路、Rho家族激酶、Src激酶、PI3激酶和Smad通路参与调控上皮细胞转分化过程。肾小管上皮细胞在病理条件下可转分化为肌成纤维细胞 ,其细胞内信号转导机制虽已有初步研究 ,但尚所知甚少。本文将就有关的研究进展及现状进行综述     

辐射对植物细胞的伤害及其修复

十余年来辐射对生物体 DNA 的损伤作用及其修复机制的研究取得了很大的进展。这不仅引起了辐射生物学者的重视,而且也引起医学和农学工作者的注意。目前在辐射生物学中是发展最快的领域之一。     

激酶调控PKB／Akt活性的机制

PKB／Akt是胞内信号转导通路网络的中心分子。活化的PKB参与多种生物学效应的调控过程,调控PKB活性作用机制的研究一直是信号转导通路领域的难点。新近的研究结果确定了若干新的调控PKB活性的激酶,从多方面解释了PKB活化和作用的分子机制。其中mTORC2、ATM和DNA—PK均通过磷酸化PKB的Ser^473位点以依赖于P13K的方式全面活化PKB;此外,其它以不依赖P13K的方式调控PKB活性的激酶包括,RET／PTC通过磷酸化PKB的Tyr^315位点、JNK通过磷酸化PKB的Thr^450。位点以及CK2通过磷酸化PKB的ser^129位点活化PKB,Brk通过磷酸化PKB的Tyr^474位点以及GRK2均可通过磷酸化PKB抑制其活性。     

紫外辐射对水生生物的影响研究进展

紫外辐射对陆生植物的生物学效应已被广泛研究,对水生生物也能产生一系列影响。本文在综述国内外紫外线在水体中渗透状况及影响因素的基础上,阐述了紫外辐射对浮游细菌和微型浮游生物、浮游植物、浮游动物、大型藻类、鱼卵和幼鱼、鱼类及两栖动物的生物学效应,从直接效应和间接效应两方面介绍了紫外辐射对水生生物作用的机理。未来研究应该注重紫外辐射与气候变化、酸沉降、水污染等环境因子联合作用对水生有机体产生影响,其研究对象应扩展至沉水植物、底栖生物等大部分水生有机体,这些研究将对深入研究水生生态系统的演化、水生生态系统退化及其修复起重要作用。     

肌动蛋白在体外与p38激酶结合并抑制其激酶活性

p38激酶(简称p38)参与炎症、应急、细胞生长与凋亡、细胞周期调控、缺血/再灌损伤及心肌肥厚等生理、病理过程中的信号转导. 为了研究该信号通道的分子机理和调节作用, 寻找p38的结合蛋白, 并检测其相互作用对激酶活性的影响, 采用体外蛋白结合试验, 在细菌内毒素或紫外辐射处理的鼠源性巨噬细胞系(RAW264.7)中, 发现有两种蛋白在体外与p38直接结合, 其中一种蛋白经肽质谱图鉴定为b-肌动蛋白(β-actin), 激酶活性检测表明, actin在体外抑制p38的自磷酸化活性, 并抑制p38对其底物ATF2的磷酸化作用. 提示actin与p38的结合在体内可能产生一种负反馈作用, 调节p38通路的信号转导, 从而调节细胞功能.     

活性氧对NF-κB活性及JNK信号通路的调节

活性氧（ROS）是生物体有氧代谢过程中产生的一类活性含氧化合物的总称,机体细胞可通过多种途径维持ROS产生与降解的动态平衡。研究表明,活性氧可作为第二信使调节与细胞增殖、分化、凋亡相关的信号转导通路。c-JunN端激酶（JNK）通路可以介导氧化应激、细胞因子、紫外照射等引起的细胞凋亡。另外,κ基因结合核因子（NF-κB）是氧化应激调节的靶因子之一,同样也能诱导促进细胞内的氧化应激反应,还可通过活性氧蓄积抑制JNK的激活。简要综述活性氧对NF-κB和JNK信号通路的调节。     

PI3K/Akt信号通路相关的生物学调控机制研究进展

PI3K/Akt信号通路是由酶联受体介导的信号转导通路,该通路不仅参与多种生长因子、细胞因子和细胞外基质等的信号转导,同时还参与细胞增殖、分化、凋亡和葡萄糖转运等多种细胞功能的调节,特别是在细胞凋亡、细胞存活以及调控细胞糖代谢等方面具有重要作用。本研究综述了PI3K-Akt信号通路的结构组成、通路活化、通信过程、调控机制及其生物学功能等方面的研究进展,为进一步研究PI3K/Akt信号通路的生物学调控作用机制提供启示。     

Solar ultraviolet radiation-induced DNA damage in aquatic organisms: potential environmental impact

Continuing depletion of stratospheric ozone and subsequent increases in deleterious ultraviolet (UV) radiation at the Earth's surface have fueled the interest in its ecological consequences for aquatic ecosystems. The DNA is certainly one of the key targets for UV-induced damage in a variety of aquatic organisms. UV radiation induces two of the most abundant mutagenic and cytotoxic DNA lesions, cyclobutane pyrimidine dimers (CPDs) and pyrimidine pyrimidone photoproducts (6-4PPs) and their Dewar valence isomers. However, aquatic organisms have developed a number of repair and tolerance mechanisms to counteract the damaging effects of UV on DNA. Photoreactivation with the help of the enzyme photolyase is one of the most important and frequently occurring repair mechanisms in a variety of organisms. Excision repair, which can be distinguished into base excision repair (BER) and nucleotide excision repair (NER), also play an important role in DNA repair in several organisms with the help of a number of glycosylases and polymerases, respectively. In addition, mechanisms such as mutagenic repair or dimer bypass, recombinational repair, cell-cycle checkpoints, apoptosis and certain alternative repair pathways are also operative in various organisms. This review deals with the UV-induced DNA damage and repair in a number of aquatic organisms as well as methods of detecting DNA damage.     

紫外线辐射对蓝藻细胞活性的影响

紫外线辐射 2种蓝藻Anabaena 6 3l和Anabaenaazollae不同时间 ,用UV30 0 0分光光度计测定活体连续吸收光谱 ,并测定细胞存活率。结果发现紫外线辐射对这 2种蓝藻的光合色素有不同程度的破坏作用 ;紫外线辐射 2min左右就可以杀死全部的A .6 3l和A .azollae细胞。实验还证实了小剂量刺激效应的存在。     

Molecular response to climate change: temperature dependence of UV-induced DNA damage and repair in the freshwater crustacean Daphnia pulicaria

In temperate lakes, asynchronous cycles in surface water temperatures and incident ultraviolet (UV) radiation expose aquatic organisms to damaging UV radiation at different temperatures. The enzyme systems that repair UV‐induced DNA damage are temperature dependent, and thus potentially less effective at repairing DNA damage at lower temperatures. This hypothesis was tested by examining the levels of UV‐induced DNA damage in the freshwater crustacean Daphnia pulicaria in the presence and absence of longer‐wavelength photoreactivating radiation (PRR) that induces photoenzymatic repair (PER) of DNA damage. By exposing both live and dead (freeze‐killed) Daphnia as well as raw DNA to UV‐B in the presence and absence of PRR, we were able to estimate the relative importance and temperature dependence of PER (light repair), nucleotide excision repair (NER, dark repair), and photoprotection (PP). Total DNA damage increased with increasing temperature. However, the even greater increase in DNA repair rates at higher temperatures led net DNA damage (total DNA damage minus repair) to be greater at lower temperatures. Photoprotection accounted for a much greater proportion of the reduction in DNA damage than did repair. Experiments that looked at survival rates following UV exposure demonstrated that PER increased survival rates. The important implication is that aquatic organisms that depend heavily on DNA repair processes may be less able to survive high UV exposure in low temperature environments. Photoprotection may be more effective under the low temperature, high UV conditions such as are found in early spring or at high elevations.     

Photooxidation and antioxidant responses in the earthworm Amynthas gracilis exposed to environmental levels of ultraviolet B radiation

Ultraviolet (UV) radiation leads to photooxidation in various organisms. Our previous study demonstrated that ultraviolet B (UV-B) radiation is lethal for particular species of earthworms, but the mechanisms responsible for the lethality are unclear. In our current study, we investigated that ultraviolet light causes photooxidative damage and reduces antioxidant responses in the earthworm Amynthas gracilis. Intact earthworms and skin/muscle tissue extracts were exposed to UV-B radiation for in vivo and in vitro studies. Both in vitro and in vivo results showed that the products of photooxidative damage, MDA and H₂O₂, increased after UV-B exposure. Glutathione peroxidase (GPx) and catalase were inhibited immediately after exposure to high doses (3000 J/m²) of UV-B radiation in vivo. Catalase activity was increased following a low UV-B dose (500 J/m²) in vivo, but decreased in response to all dosage levels in vitro. These data indicate that a relationship exists between UV-B induced damage and photooxidation and also that catalase and GPx act as important antioxidants to prevent photooxidation. According to these data, A. gracilis exhibits high sensitivity to environmental levels of UV-B. Therefore, A. gracilis represents a sensitive and cost-effective model organism for investigations of UV-radiation damage and environmental UV stress.     

Development in the Floating World: Defenses of Eggs and Embryos Against Damage from UV Radiation

Eggs and embryos of many aquatic organisms develop in the watercolumn and can experience ultraviolet radiation with potentiallydeleterious effects. This is especially vexing for floatingembryos that develop in the surface or neuston layer. Radiationdamage can be a particular problem for these embryos since thecell division cycle during the cleavage period is quite shortand often these cycles do not have mitotic checkpoints to insurefaithful transmission of DNA to the daughter cells. This couldresult in cell division with unrepaired DNA in the blastomeres,which could impact embryogenesis and the transmission of thegenome through the germ line. Described strategies to restrictradiation damage include mechanisms to limit oxidative damageand the use of sunscreens such as the mycosporines to curb radiationto sensitive targets. We describe a particularly ingenious useof sunscreens in the tunicate embryo, the use of extra-embryoniccells to shield the embryo from potentially harmful UV-A andUV-B radiation. We also raise questions regarding the natureof UV damage to embryos (is it DNA or also protein) and thecharacteristics of DNA repair in such embryos. It is likelythat unique mechanisms are present in floating embryos thatdevelop in this air-water interface to assure that cell andgenomic integrity are maintained in this challenging environment.     

High probability of disrupting a disulphide bridge mediated by an endogenous excited tryptophan residue

It is well known that ultraviolet (UV) radiation may reduce or even abolish the biological activity of proteins and enzymes. UV light, as a component of sunlight, is illuminating all light-exposed parts of living organisms, partly composed of proteins and enzymes. Although a considerable amount of empirical evidence for UV damage has been compiled, no deeper understanding of this important phenomenon has yet emerged. The present paper presents a detailed analysis of a classical example of UV-induced changes in three-dimensional structure and activity of a model enzyme, cutinase from Fusarium solani pisi. The effect of illumination duration and power has been investigated. A photon-induced mechanism responsible for structural and functional changes is proposed. Tryptophan excitation energy disrupts a neighboring disulphide bridge, which in turn leads to altered biological activity and stability. The loss of the disulphide bridge has a pronounced effect on the fluorescence quantum yield, which has been monitored as a function of illumination power. A general theoretical model for slow two-state chemical exchange is formulated, which allows for calculation of both the mean number of photons involved in the process and the ratio between the quantum yields of the two states. It is clear from the present data that the likelihood for UV damage of proteins is directly proportional to the intensity of the UV radiation. Consistent with the loss of the disulphide bridge, a complex pH-dependent change in the fluorescence lifetimes is observed. Earlier studies in this laboratory indicate that proteins are prone to such UV-induced radiation damage because tryptophan residues typically are located as next spatial neighbors to disulphide bridges. We believe that these observations may have far-reaching implications for protein stability and for assessing the true risks involved in increasing UV radiation loads on living organisms.     

Ultraviolet radiation screening compounds

Amongst the diversity of methods used by organisms to reduce damage caused by ultraviolet (UV) radiation, the synthesis of UV-screening compounds is almost ubiquitous. UV-screening compounds provide a passive method for the reduction of UV-induced damage and they are widely distributed across the microbial, plant and animal kingdoms. They share some common chemical features. It is likely that on early earth strong selection pressures existed for the evolution of UV-screening compounds. Many of these compounds probably had other physiological roles, later being selected for the efficacy of UV screening. The diversity in physiological functions is one of the complications in studying UV-screening compounds and determining the true ecological importance of their UV-screening role. As well as providing protection against ambient UV radiation, species with effective screening may also be at an advantage during natural ozone depletion events. In this review the characteristics of a wide diversity of UV-screening compounds are discussed and evolutionary questions are explored. As research into the range of UV-screening compounds represented in the biosphere continues, so it is likely that the properties of many more compounds will be elucidated. These compounds, as well as providing us with insights into natural responses to UV radiation, may also have implications for the development of artificial UV-screening methods to reduce human exposure to UV radiation.     

Photoprotection of DNA (in vitro) by acyclothymidine dinucleosides

Excessive exposure to sunlight is primarily implicated in ultraviolet (UV) induced skin cancers worldwide. Direct absorption of UV radiation by DNA leads to the formation of cyclobutane pyrimidine dimers (CPDs) resulting in DNA damage. The molecular mechanisms involved in the mutagenicity of CPDs are well established. Photoprotection of the skin from the detrimental effects of UV is essential in preventing skin damage. A variety of formulations, which essentially contain UV filters have been used as photoprotective agents of the skin. These comprise aromatic and inorganic molecules, whose mechanism of action involves either absorption, reflection, or scattering of UV radiation. However, the downstream photoproducts of some of these molecules have undesirable characteristics which compromise their utility. A biomimetic approach involving structural analogs of nucleic acids can help overcome these limitations. Herein, we show the photoprotective action of acyclothymidine dinucleosides on both plasmid and cellular DNA.     

An Arabidopsis Mutant Tolerant to Lethal Ultraviolet-B Levels Shows Constitutively Elevated Accumulation of Flavonoids and Other Phenolics

The isolation and characterization of mutants hypersensitive to ultraviolet (UV) radiation has been a powerful tool to learn about the mechanisms that protect plants against UV-induced damage. To increase our understanding of the various mechanisms of defense against UVB radiation, we searched for mutations that would increase the level of tolerance of Arabidopsis plants to UV radiation. We describe a single gene dominant mutation (uvt1) that leads to a remarkable tolerance to UVB radiation conditions that would kill wild-type plants. Pigment analyses show a constitutive increase in accumulation of UV-absorbing compounds in uvt1 that increases the capacity of the leaves to block UVB radiation and therefore is likely to be responsible for the elevated resistance of this mutant to UVB radiation. These increases in absorption in the UV region are due, at least in part, to increases in flavonoid and sinapate accumulation. Expression of chalcone synthase (CHS) mRNA was shown to be constitutively elevated in uvt1 plants, suggesting that the increases in absorption may be a consequence of changes in gene expression. Expression of CHS in uvt1 was shown to be still inducible by UV, indicating that the uvt1 lesion may not affect the UV-mediated regulation of CHS gene expression. Our data support an important role for UV screens in the overall protection of plants to UVB radiation. The uvt1 mutant could prove to be an important tool to elucidate further the exact role of UV-absorbing pigments in UV protection as well as the relative contribution of other mechanisms to the overall tolerance of plants to UV radiation.     

ULTRAVIOLET SUNSCREENS IN GYMNODINIUM SANGUINEUM (DINOPHYCEAE): MYCOSPORINE-LIKE AMINO ACIDS PROTECT AGAINST INHIBITION OF PHOTOSYNTHESIS

Marine phytoplankton are sensitive to inhibition of photosynthesis by solar ultraviolet (UV) radiation, although sensitivity varies, depending on the growth environment. A mechanism suggested to increase resistance to UV inhibition is the accumulation of UV-absorbing compounds, such as the mycosporine-like amino acids (MAAs) found in many marine organisms. However, the effectiveness of these compounds as direct optical screens in microorganisms has remained unclear. The red-tide dinoflagellate Gymnodinium sanguineum Hirasaka accumulates about 14-fold more MAAs (per unit of chlorophyll) in high (76 W·m⁻²) than in low (15 W·m⁻²) growth irradiance. Biological weighting functions were estimated for UV inhibition of photosynthesis and showed that the high-light-grown cultures have lower sensitivity to UV radiation at wavelengths strongly absorbed by the MAAs. The time course of photosynthesis during exposure to UV radiation was measured using pulsed amplitude modulated (PAM) fluorometry and displayed a steady-state level after 15 min of exposure, indicating active repair of damage to the photosynthetic apparatus. Repair was blocked in the presence of the antibiotic streptomycin, yet high-light G. sanguineum remained less sensitive to UV radiation than did low-light cultures. These experiments show that MAAs act as spectrally specific UV sunscreens in phytoplankton.