蓝细菌光敏色素的分子结构、生物合成和可逆光致变色效应

蓝细菌光敏色素(CBCRs)是蓝细菌中感受光的重要光受体,能够响应从紫外光到红外光范围内的光信号,进而影响蓝细菌的光化学行为。蓝细菌光敏色素通过N-末端GAF(cGMP phosphodiesterase,adenylyl cyclase and FhlA domain)结构域中保守性半胱氨酸共价结合藻胆色素,形成具有感光生理功能的色素蛋白质。本文重点在分子水平上综述了蓝细菌光敏色素的分子结构、生物合成和可逆光致变色效应机理,并基于最新的研究进展,就蓝细菌光敏色素今后的研究方向进行了展望。     

光敏色素光转化生理学特性研究进展(英文)

植物主要光受体光敏色素调节植物的多种光调控,使其作出最适宜的光生长,如:光形态建成.光敏色素接受光信号的生物功能基于其红光吸收型(Pr)和具有生理活性的远红光吸收型(Pfr)之间的光可逆式光转化.依据光生物学的标准该转化过程与光合作用相比是一个低能光反应过程,而且其间产生的中间过渡态和光敏色素的亚库可能反过来影响光转化的过程而最终表现出生理功能.在此,主要综述了近年来运用时间分辨动力学特别是差分荧光和光化学,研究光敏色素及其中间过度态光生物物理和光生物化学特性的若干进展,讨论了光信号转导的原初光反应的机理.     

Tween-80胶束对苝醌类光敏剂基态和激发态的保护作用

用Tween-80非离子型胶束增溶竹红菌甲素、乙素(HA、HB)及金丝桃蒽酮(HYP)等苝醌类光敏剂,发现该胶束对HA的基态和激发态都有保护作用.相对于含水有机体系,HA在胶束中基态的pKa值升高,荧光量子产率增大,光敏反应产生的活性中间体1O2和·0H的产额增加,从而提高了其光敏活性,这在光敏损伤作用中具有重要的生物学意义.实验还发现,Tween-80胶束对HB及HYP的保护作用与HA类似,而且保护作用与苝醌的结构有关,这对筛选光敏剂作为光疗药物具有指导作用.     

细胞外ATP对低温下菜豆叶片光系统Ⅱ运行及光能分配的影响

细胞外ATP(eATP)可作为一种重要的胞外分子调节植物的多种生理反应。该研究以菜豆(Phaseolus vulgaris L.)品种‘农普12号’幼苗叶片为实验材料,研究了胞外1.0mmol/L ATP溶液对低温下(10℃、10h)菜豆叶片光系统Ⅱ(PSⅡ)运行及光能分配的影响。结果显示:(1)低温胁迫(10℃、10h)对菜豆叶片PSⅡ的潜在最大光化学效率(F_v/F_m)没有产生显著性影响,但低温胁迫却降低了叶片的实际光化学运行效率[Y(Ⅱ)],同时降低了PSⅡ的光化学反应能量(P),增加了天线热耗散能量(D)和非光化学反应耗散能量(E),使叶片胞外ATP水平有所下降。(2)叶片施加外源ATP可以有效缓解低温胁迫下菜豆叶片胞外ATP水平的下降,同时使叶片的实际光化学效率[Y(Ⅱ)]和光化学反应能量(P)显著上升,也使天线热耗散能量(D)非光化学反应耗散能量(E)均显著下降。研究表明,低温胁迫降低了菜豆叶片PSⅡ的光化学运行并增加了光能的耗散,而在低温胁迫下增加胞外ATP水平能够有效提高菜豆叶片光化学反应的运行效率并降低光能的耗散。     

越冬期广玉兰阳生叶和阴生叶PSⅡ功能及捕光色素分子内禀特性的比较研究

捕光色素分子的内禀特性不仅决定了光能的吸收与传递,也将影响到激发能向光化学反应、热耗散和叶绿素荧光的分配。本文采用叶绿素荧光技术和光合电子流对光响应机理模型,研究了越冬期广玉兰（Magnolia grandiflora）阳生叶和阴生叶两种不同光环境下叶片PSⅡ功能及其捕光色素分子内禀特性的差异,以探索广玉兰越冬的光保护策略。结果表明：越冬期低温导致叶片轻微光抑制的发生,全光照加剧了阳生叶光抑制程度,而弱光环境有利于阴生叶光抑制的恢复。阳生叶可通过降低叶绿素含量和捕光色素分子数量以减少对光能的吸收,并且具有较强的光化学和热耗散能力以保护光合机构免受低温强光伤害。而阴生叶虽然其光化学反应能力相对较弱,但具有较强的热耗散能力,可有效地保护其免受短时曝露在强光下的伤害。     

外源6-BA对低温胁迫下茄子幼苗光合作用、叶绿素荧光参数及光能分配的影响

本文研究了外源6-BA对低温胁迫下茄子幼苗光合作用、叶绿素荧光参数和能量分配的影响。结果表明,外源6．BA显著增加了低温胁迫下茄子叶绿素含量、净光合速率（Pn）、蒸腾速率（t）、气孔导度（Gs）和胞间CO2浓度（c1）;同时外源6-BA明显提高了低温胁迫下茄子幼苗叶片的PSⅡ最大光化学效率（Fv/Fm）、PSⅡ潜在活性（R／Fo）、PSII天线转化效率（FvFm）、实际光化学效率（φpsⅡ）、光化学猝灭系数（g,）和光化学反应能量（P）,降低了非光化学猝灭系数（NPQ）、天线热耗散能量（D）,对非光化学反应耗散能量（E）无明显影响。表明外源6-BA处理通过促进低温胁迫下茄子幼苗光合作用,提高光合电子传递效率,从而保护光合系统,降低低温胁迫对植物的损伤。     

光化学法灭活血液中病毒的研究进展

光化学灭活法是指某些化学光敏剂与病原微生物的核酸或蛋白结合后,再以特定波长光照射,使光敏剂与核酸或蛋白之间发生光化学反应,以导致病原体失活的方法。研究认为,补骨脂素光化学法既可灭活细胞外的游离病毒,又可灭活细胞内的病毒,对包膜和无包膜病毒都有效。而部花青５４０、血卟啉和甲基蓝等光化学法主要对包膜病毒灭活效果较好。不同光化学灭活法对血液成分的影响程度有差异     

鱼类神经行为毒性研究进展

神经行为毒性是神经科学、神经药理学和神经毒理学的重要研究内容,对评价生态系统质量和研究有害因素或药物在生物神经系统作用机制具有重要理论和应用价值。鱼类中枢神经系统发达,对水环境中化合物极为敏感,其神经系统能够对各种刺激产生综合协调的应答反应,影响其运动功能、应激反应以及学习/记忆,改变游泳行为和社会行为,产生神经行为异常,诱发神经行为毒性效应。近年来,许多研究者开展了一系列以鱼类为受试对象的神经行为毒性研究,表明鱼类是开展神经行为毒性研究的重要物种,其成果在生态环境监测和评价、渔业生产、神经系统机制探究及药物开发等方面得到了广泛应用。鱼类作为神经行为毒性研究的物种,补充经典哺乳动物模型的不足,提供了高通量体外细胞分析和经典哺乳动物模型之间的关键模型。文章从鱼类生物学特征、实验鱼类品系和全基因组测序3个方面阐明鱼类是开展神经行为毒性研究的重要物种,综述了微塑料及其吸附污染物、有机污染物2类典型污染物和酒精、咖啡因、苯二氮卓类药物、选择性血清素再吸收抑制剂4类药物对鱼类的游泳行为和社会行为影响,探讨鱼类产生剂量或时间依赖性的神经行为毒性效应,并对未来研究方向进行了分析展望,以期为神经行为毒...     

匹伐他汀临床应用的最新进展

匹伐他汀(pitavastatin)是新一代人工合成的降血脂类药物。该药是新一代HMG-COA还原酶抑制剂,用于治疗原发型高脂血症和混合型血脂障碍,能够显著降低LDL、TC、TG、及升高HDL-C。药物动力学性质优良,具有肝细胞选择性,并且毒性低,安全性好,具有抗动脉粥样硬化、促进血管生成和抗炎作用。本文就匹伐他汀的临床研究进展进行综述。     

光动力疗法联合声动力疗法在抗肿瘤方面的研究进展

光动力疗法是一种使用光敏药物和激光活化治疗肿瘤疾病的方法.用特定波长的光辐照肿瘤部位,能使选择性聚集在肿瘤组织的光敏药物活化,引发光化学反应破坏肿瘤.然而,光动力疗法在临床上的应用却一直存在治疗深度受限的问题.本文分析了光动力疗法在临床应用中的局限性,并指出光动力疗法联合声动力疗法是一种可以克服光动力疗法治疗深度局限性...     

Reliable Screening of Dye Phototoxicity by Using a Caenorhabditis elegans Fast Bioassay

Phototoxicity consists in the capability of certain innocuous molecules to become toxic when subjected to suitable illumination. In order to discover new photoactive drugs or characterize phototoxic pollutants, it would be advantageous to use simple biological tests of phototoxicy. In this work, we present a pilot screening of 37 dyes to test for phototoxic effects in the roundworm Caenorhabditis elegans. Populations of this nematode were treated with different dyes, and subsequently exposed to 30 min of white light. Behavioral outcomes were quantified by recording the global motility using an infrared tracking device (WMicrotracker). Of the tested compounds, 17 dyes were classified as photoactive, being phloxine B, primuline, eosin Y, acridine orange and rose Bengal the most phototoxic. To assess photoactivity after uptake, compounds were retested after washing them out of the medium before light irradiation. Dye uptake into the worms was also analyzed by staining or fluorescence. All the positive drugs were incorporated by animals and produced phototoxic effects after washing. We also tested the stress response being triggered by the treatments through reporter strains. Endoplasmic reticulum stress response (hsp-4::GFP strain) was activated by 22% of phototoxic dyes, and mitochondrial stress response (hsp-6::GFP strain) was induced by 16% of phototoxic dyes. These results point to a phototoxic perturbation of the protein functionality and an oxidative stress similar to that reported in cell cultures. Our work shows for the first time the feasibility of C. elegans for running phototoxic screenings and underscores its application on photoactive drugs and environmental pollutants assessment.     

Broad-spectrum sunscreens prevent the secretion of proinflammatory cytokines in human keratinocytes exposed to ultraviolet A and phototoxic lomefloxacin

The combination of phototoxic drugs and ultraviolet (UV) radiation can trigger the release of proinflammatory cytokines. The present study measured the ability of sunscreens to prevent cytokine secretion in human keratinocytes following cotreatment of these cells with a known photoreactive drug and UVA. Keratinocytes were treated for 1 h with increasing concentrations of lomefloxacin (LOM) or norfloxacin (NOR), exposed to 15 J/cm2 UVA, and incubated for 24 h. NOR, owing to the absence of a fluorine atom in position 8, was non-phototoxic and used as a negative control. Cell viability and the release of 3 cytokines were assessed, namely interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha). The measurement of these cytokines may be a useful tool for detecting photoreactive compounds. To measure their ability to prevent cytokine secretion, various sunscreens were inserted between the UVA source and the cells. Treatment with NOR, NOR plus UVA, or LOM had no effect on the cells. LOM plus UVA, however, had an effect on cell viability and on cytokine secretion. IL-1alpha levels increased with LOM concentration. The release of TNF-alpha and IL-6 followed the same pattern at lower concentrations of LOM but peaked at 15 micromol/L and decreased at higher concentrations. Sunscreens protected the cells from the effects of LOM plus UVA, as cell viability and levels of cytokines remained the same as in the control cells. In conclusion, the application of broad-spectrum sunscreen by individuals exposed to UVA radiation may prevent phototoxic reactions initiated by drugs such as LOM.     

Role of flavonoids in controlling the phototoxicity of Hypericum perforatum extracts.

Hypericum perforatum extracts are used mainly as oral antidepressants. Depending on source the extracts contain various amounts of phenylpropanes, flavonol derivates, biflavones, proathocyanidines, xanthones, phloroglucinoles, some amino acids, naphtodianthrones (hypericines) and essential oil constituents. The therapeutic use of Hypericum perforatum extracts however is limited by their phototoxic potential. It was the aim of the present study to investigate the phototoxic potential of 3 Hypericum perforatum extracts from different sources as well as some of its main constituents. In order to systematically study the phototoxic potential we established a modified neutral red assay utilizing an immortalized human keratinocyte cell line (HaCaT cells) as substrate and UVA irradiation. This modified neutral red assay was found to be a simple and reliable method for detecting phototoxic effects of reference agents and plant extracts. The validity of this method was demonstrated with known phototoxic compounds like chloropromazine and psoralenes like 5-MOP. Hypericum perforatum extracts demonstrated cytotoxicity and photocytotoxicity in a dose and UVA-dose dependent manner. Hypericine itself also evoked severe phototoxic effects and was thus identified as the main phototoxic constituent. Among the tested flavonoids quercitrin was found to be cytotoxic, while rutin unexpectedly demonstrated phototoxicity whereas quercitrin was effective to control the phototoxic activity of Hypericum perforatum extracts.     

DNA repair inhibition by UVA photoactivated fluoroquinolones and vemurafenib

Cutaneous photosensitization is a common side effect of drug treatment and can be associated with an increased skin cancer risk. The immunosuppressant azathioprine, the fluoroquinolone antibiotics and vemurafenib—a BRAF inhibitor used to treat metastatic melanoma—are all recognized clinical photosensitizers. We have compared the effects of UVA radiation on cultured human cells treated with 6-thioguanine (6-TG, a DNA-embedded azathioprine surrogate), the fluoroquinolones ciprofloxacin and ofloxacin and vemurafenib. Despite widely different structures and modes of action, each of these drugs potentiated UVA cytotoxicity. UVA photoactivation of 6-TG, ciprofloxacin and ofloxacin was associated with the generation of singlet oxygen that caused extensive protein oxidation. In particular, these treatments were associated with damage to DNA repair proteins that reduced the efficiency of nucleotide excision repair. Although vemurafenib was also highly phototoxic to cultured cells, its effects were less dependent on singlet oxygen. Highly toxic combinations of vemurafenib and UVA caused little protein carbonylation but were nevertheless inhibitory to nucleotide excision repair. Thus, for three different classes of drugs, photosensitization by at least two distinct mechanisms is associated with reduced protection against potentially mutagenic and carcinogenic DNA damage.     

UV-mediated antibiotic activity of some compositae species

Roots, leaves, and flowers of 80 species of Compositae were tested for phototoxic activity against Candida albicans. Many genera showed activity, especially in the roots. No active genera were found in the tribe Cichorieae. Phototoxic compounds were isolated from Chrysanthemum leucanthemum florets and Cirsium arvense roots. Chemotaxonomic evidence plus preliminary chemical data suggests that the compounds are polyacetylenic in nature. Unlike other phototoxic compounds, these are inactive against human skin.     

Drug-induced photosensitivity: phototoxic and photoallergic reactions--a few molecular aspects

Drug-induced photosensitivity involves mainly phototoxic and photoallergic reactions. The main features of phototoxic and photoallergic reactions are presented and some molecular aspects involved in the mechanisms leading to an adverse skin response are illustrated with examples.     

Influence of light on plant allelochemicals: A synergistic defense in higher plants

Plant phototoxins are broad-spectrum biocides which adversely affect an array of potential plant enemies, including among others disease-causing pathogens, nematodes, insect herbivores, and competing plant species. Thus far, plants which contain these broad-spectrum allelochemicals have been found to occur in open habitats (i.e., in full sunlight) where a defensive mechanism mediated by light would seem to operate most effectively. The levels of available light in shaded environments, although considerably lower than full sun (1–10% of full sun), are equivalent to the intensities of light used to kill phototoxin-treated insects in laboratory studies. This suggests that phototoxic reactions might mediate important organismal interactions in shaded environments as well. In this study, more than 230 Costa Rican rainforest plants were bioassayed for phototoxic metabolites in an effort to ascertain their prevalence among plants growing in moderate to extreme shade. Microbial bioassays, employing Bacillus cereus (a gram positive bacterium), Escherichia coli (a gram negative bacterium), and Saccharomyces cerevisiae (a yeast) were used to rapidly and sensitively indicate phototoxic action and potential for insecticidal action. Tissue extracts from 12 plant families tested positive for phototoxins. This is the first report of phototoxins occurring in eight of those families (Acanthaceae, Campanulaceae, Gesnariaceae, Loganiaceae, Malpigaceae, Phytolaccaceae, Piperaceae, and Sapotaceae). The presence of phototoxins in rainforest plants suggests that phototoxic plant allelochemicals may function as important defenses in low-light, as well as high-light, environments.     

Melasma--updated treatments

Melasma is a common, acquired facial skin disorder, mostly involving sun-exposed areas like cheeks, forehead and upper lip. Melasma occurs in both sexes, although almost 90 percent of the affected are women. It is more common in darker skin types (Fitzpatrick skin types IV to VI) especially Hispanics/Latinos, Asians and African-Americans. The onset of the melasma is at puberty or later, with exception of darker skin types, who tend to develop this problem in the first decade of life. The etiology is still unknown, although there are a number of triggering factors related to the onset of melasma. The most important are sun-exposure and genetic factors in both sexes, while hormonal activity has more important role in females. In addition, stress and some cosmetic products and drugs containing phototoxic agents can cause outbreaks of this condition. Melasma should be treated using monotherapies or combination of therapy, mainly fixed triple or dual combinations containing hydroquinone, tretinoin, corticosteroids or azelaic acid. Modified Kligman's formula is also very effective. Above mentioned therapy regimens in combination with UVA and UVB blocking sunscreens are mostly effective in epidermal melasma. Discontinuation of the use of birth control pills, scented cosmetic products, and phototoxic drugs coupled with UV protection are also benefitial in clearing of melasma. Alternative treatment including chemical peels and glicolic acid, seem to have the best result as a second line treatment after bleaching creams. Laser treatments show limited efficacy and should rarely be used in the treatment of melasma. Combining topical agents like hydroquinone, tretinoin and a corticosteroid in addition to sun avoidance, regular use of sunscreen throughout the year and patient education is the best treatment in this difficult to treat condition.     

Contrasting action of flavonoids on phototoxic effects induced in human skin fibroblasts by UVA alone or UVA plus cyamemazine, a phototoxic neuroleptic.

The potential protective effects of the flavanol catechin, the flavonol quercetin, the flavones, luteolin and rutin, and the isoflavones, genistein and daidzein, against the photo-oxidative stress induced by ultraviolet A radiation (UVA) and by phototoxic reactions resulting from the interaction of UVA with drugs and chemicals, has been assessed with cultured human skin fibroblasts. Lipid peroxidation and cell death have been chosen as model photobiological damage induced by UVA alone or photosensitized by cyamemazine (CMZ) and its photoproduct possessing phototoxic properties. Contrasting effects of flavonoids are observed. The flavanol, the flavonol and the flavones may protect against lipid peroxidation and cell death induced by 30 J cm(-2) of UVA alone or CMZ plus 10 J cm(-2) UVA. On the other hand, an amplification of the photodamage may be observed with isoflavones. A concentration-dependence study demonstrates that among the protective flavonoids, quercetin is the most efficient. The very effective protection brought by quercetin may result from its ability to scavenge reactive oxygen species produced by the photo-oxidative stress. However, the modification of membrane properties and the alteration of the lysosomal function by quercetin may not be neglected in these protective effects. The amplification of the photodamage by isoflavones is in sharp contrast with previous literature data demonstrating photoprotection by genistein. As a consequence, it may be concluded that an eventual antioxidant action of genistein may strongly depend on cells and photosensitizers. Furthermore such contrasting pro-versus anti-oxidant effects have to be taken into account when using flavonoid mixtures of plant extracts.     

Phototoxicity of the fluorescent membrane dyes PKH2 and PKH26 on the human hematopoietic KG1a progenitor cell line.

BACKGROUND: The phototoxic effects of the well-known fluorescent membrane dyes PKH2 and PKH26 have been unknown, although their use in cell tracking experiments has increased dramatically. To eliminate the phototoxicity-induced alteration in cell function and morphology, it is essential to examine the suspicious phototoxicity of these dyes. METHODS: Chemical and phototoxic effects of PKH dyes on the human hematopoietic KG1a cell line were examined. To minimize phototoxicity in long-term cell tracking experiments lasting up to 18 h with a fluorescence microscope system, time-lapse monitoring with different time intervals and exposure times was introduced. RESULTS: There were no significant effects of the two PKH dyes on cell viability and growth when using dye concentrations up to 5 microM. However, when stained cells were exposed to excitation light, cell viability decreased dramatically, showing the phototoxicity of the PKH dyes. More than 60% of cells stained with 5 microM PKH26 died after 5 min of continuous light exposure. The phototoxic effect was more extensive in cells stained with higher concentrations of the dyes. CONCLUSIONS: We present guidelines for the optimal use of these dyes by using a defined hardware configuration.