Biomolecular proteomics discloses ATP synthase as the main target of the natural glycoside deglucoruscin

2016 ◽  
Vol 12 (10) ◽  
pp. 3132-3138 ◽  
Author(s):  
Federica del Gaudio ◽  
Carmen Festa ◽  
Matteo Mozzicafreddo ◽  
Michele Vasaturo ◽  
Agostino Casapullo ◽  
...  

Extracts ofRuscus aculeatusare rich of deglucoruscin, a spirostanol glycoside, which is able to interact with ATP synthase and modulate its activity.

1972 ◽  
Vol 70 (2) ◽  
pp. 385-395 ◽  
Author(s):  
B. K. Davis ◽  
I. Noske ◽  
M. C. Chang

ABSTRACT Mature female hamsters bearing subcutaneous polyacrylamide (PAA) implants, with ethinyloestradiol (EO), for at least 10 days prior to mating revealed: 0.5 and 2.5 mg EO in 7% PAA significantly disturb the timing of oestrus and mating, but have no apparent effect on rate of pregnancy, ovulation and implantation. 2.5 mg EO in 20 and 40% PAA conspicuously reduces the likelihood of pregnancy, although the occurrence of oestrus and mating are affected only slightly. Fertility in these hamsters was virtually restored, judging from pregnancy rates, when they were remated 11 days, or more, following removal of their implants (37 days after implantation), but significantly more foetuses were resorbed in these litters. From tissue sections of skin and muscle at the implant site, ovary, uterus, pituitary, adrenals and liver, PAA implants, without EO, cause no overt pathological changes in the bearer. Effects characteristic of oestrogen are present when these implants contain EO, and these include a conspicuous thickening of the epidermis and dermis; haemorrhagic lesions were also noted in the maternal placenta of animals with EO implants. There is an association between reproductive performance and the rate of EO release by an implant. A 7% PAA implant with 2.5 mg EO can release most of it within 2 days, and principally influences events (oestrus and mating) that precede the main target (pregnancy) of a 20% PAA implant, which releases the steroid over the longer interval of 7 days.


Author(s):  
Ю.И. Кирова ◽  
Э.Л. Германова

Митохондриогенез и ангиогенез являются ключевыми нейропротекторными механизмами, повышающими устойчивость нервной ткани к условиям гипоксии/ишемии. В настоящее время фармакологическая индукция биогенеза митохондрий является одним из наиболее перспективных и активно разрабатываемых подходов к коррекции ишемических и постишемических нарушений, нейродегенеративных заболеваний и кардиопатий. Выявление факта стимуляции митохондриогенеза эталонными нейропротекторными препаратами позволит существенно расширить представление об их терапевтическом потенциале и принципах применения. Цель исследования - изучение влияния нейропротекторного сукцинатсодержащего препарата мексидол на экспрессию каталитических субъединиц дыхательных ферментов митохондрий, АТФ-синтазы и фактора роста эндотелия сосудов в коре головного мозга крыс с врожденными различиями в устойчивости к дефициту кислорода. Методика. Исследование выполнено на белых беспородных крысах-самцах. Инъекции мексидола (40 мг/кг, внутрибрюшинно) выполняли ежедневно на протяжении 20 сут. Уровень экспрессии каталитических субъединиц дыхательных ферментов митохондрий и АТФ-синтазы, фактора роста эндотелия сосудов и сукцинатного рецептора в ткани коры головного мозга оценивали методом иммуноблоттинга. Общую резистентность организма к острой гипоксии тестировали в гипобарической камере проточного типа при разрежении атмосферы, соответствующем 190 мм рт. ст. (3% О). Результаты. В ходе курса применения мексидола происходило увеличение уровня каталитических субъединиц дыхательных ферментов митохондрий (NDUFV2, SDHA, cyt b, COX1), АТФ-синтазы (ATP5A), фактора роста эндотелия сосудов (VEGF) и сукцинатного рецептора (SUCNR1), особенно выраженное у неустойчивых к гипоксии особей. Заключение. Впервые показана вовлеченность сукцинатсодержащего препарата мексидол в механизмы индукции ферментов энергопродуцирующей системы митохондрий коры головного мозга, что существенно расширяет сложившиеся представления о механизмах его энерготропного действия. Mitochondriogenesis and angiogenesis are crucial neuroprotective mechanisms that increase the resistance of nervous tissue to hypoxia/ischemia conditions. Currently, pharmacological induction of mitochondrial biogenesis is one of the most promising and actively developed approaches for the correction of ischemic and post-ischemic disorders, neurodegenerative diseases and cardiopathies. Revealing the fact of stimulation of mitochondriogenesis with standard neuroprotective drugs will significantly expand the understanding of their therapeutic potential and principles of application. The aim of the research was to study the effect of the neuroprotective succinate-containing drug mexidol on the expression of catalytic subunits of the respiratory enzymes of mitochondria, ATP-synthase and vascular endothelial growth factor in the cerebral cortex of rats with inborn differences in resistance to oxygen deficiency. Methods. The study was carried out on white mongrel rats-males injections of mexidol (40 mg/kg, intraperitoneally) were performed daily for 20 days. The expression level of the catalytic subunits of the respiratory enzymes of mitochondria and ATP-synthase, vascular endothelial growth factor and succinate receptor in the tissue of the cerebral cortex was assessed by immunoblotting. The total resistance of the organism to acute hypoxia was tested in a hypobaric chamber with an atmosphere underpressure corresponding to 190 mm Hg (3% O). Results. During the injection course of mexidol, there was an increase in the level of catalytic subunits of the respiratory enzymes of mitochondria (NDUFV2, SDHA, cyt b, COX1), ATP-synthase (ATP5A), vascular endothelial growth factor (VEGF) and succinate receptor (SUCNR1), especially pronounced in rats with low-resistance to hypoxia. Conclusion. The study revealed for the first time the involvement of the succinate-containing drug mexidol in the mechanisms of induction of enzymes of the energy-producing system of the mitochondria of the cerebral cortex, which significantly expands the existing ideas about the mechanisms of its energy-tropic action.


Author(s):  
Valian Yoga Pudya Ardhana ◽  
Ahmad Wilda Yulianto

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