Роль молекулярных компонентов депо-зависимого тока Ca2+ – белков Stim и Orai – в лимфоцитах

In the process of evolution of eukaryotes has formatted a highly organized mechanism for maintaining and regulating intracellular calcium homeostasis, which is one of the most important components of cell signaling in all branches of the phylogenetic tree. Intracellular calcium controls numerous physiological processes in the cell. Ca2+ forms signals as their spatial-temporal distribution. The frequency and amplitude of calcium oscillations depends on the signal strength. Calcium signals causing long-term or short-term responses of cells. Mainly, calcium signals in lymphocytes mediate gene expression program initiation that leads to proliferation, differentiation and production of proinflammatory cytokines also activate formation of inflammasome. Therefore, calcium signals mediate immune, and inflammatory response, autoimmune reaction of lymphocytes. The main mechanism of calcium signaling in lymphocytes is store-dependent Ca2+ current. Mobilization of cellular Ca2+ in response to receptor stimulation commonly occurs through release of Ca2+ ions from intracellular Ca2+ stores or influx across the plasma membrane through calcium - selective channels. Calciumselective channels are assembled from two protein families: the Orai proteins which form the ion channel pore, and the stromal interaction molecule (STIM) proteins which function as endoplasmic reticulum calcium sensors and activators of the channel. Stim protein is a transmembrane monomer which is localized at the membrane of the endoplasmic reticulum. This molecule is a sensor Ca2+ in response to emptying store activates calciumselective channels the plasma membrane. These channels express proteins Orai which are tetramers forming inside the channel pore and act as a site Ca2+. Orai binds to Stim. Orai proteins are activated after receiving information from Stim about Store depletion. Thus, the relationship and coordination of Stim and Orai proteins provides store - dependent Ca2+ current and causes cellular functional responses. Increased Ca2+ levels induce the activation of transcription factors such as NFAT, JNK1, MEF2, CREB, and, in most cases, is a crucial factor in the all differentiation or death. In this review, the mechanism of the store-dependent Ca2+ current in lymphocytes is presented.В процессе эволюционного развития эукариот сформировался высокоорганизованный механизм поддержания и регуляции гомеостаза внутриклеточного кальция, который является одним из наиболее важных элементов клеточной сигнализации на всех ветвях филогенетического древа. Внутриклеточный кальций контролирует множество физиологических процессов в клетке, формируя сигналы в виде их пространственно-временного распределения, при этом сила сигнала определяет  частоту и амплитуду колебаний уровня кальция, поэтому вызывает кратковременные или долговременные ответы клеток.  Главным образом кальциевые сигналы в лимфоцитах опосредуют инициацию программы экспрессии генов, которая приводит к пролиферации, дифференциации, продукции провоспалительных цитокинов, также активируют формирование инфламмасом. Вследствие этого кальциевые сигналы опосредуют развитие инфекционного иммунитета, воспалительных ответов, аутоиммунные реакции лимфоцитов. В основе сигнальных событий лимфоцитов лежит механизм депо-зависимого тока Ca2+. Это центральный путь распространения кальциевых сигналов в клетках в ответ на высвобождение ионов из депо – эндоплазматического ретикулума – и последующей активации кальций-селективных каналов в плазматической мембране. Данный механизм обеспечивается согласованной работой белков (stromal interaction molecule) Stim и Orai.  Белок Stim представляет собой трансмембранный мономер, который локализуется в мембране эндоплазматического ретикулума. Эта молекула является  сенсором Ca2+ , в ответ на опустошение депо активирует кальций-селективные каналы плазматической мембраны. Данные каналы экспрессируют  белки Orai, которые представляют собой тетрамеры. Они формируют пору внутри канала, которая действует в качестве сайта, связывающего Ca2+. Белки Orai активируются тогда,  когда с ними  связываются белки, сигнализируя о том, что депо истощено. Таким образом, взаимосвязь и координация белков Stim и Orai обеспечивает депо-зависимый ток Ca2+ и вызывает функциональные ответы клетки. Повышение уровня Ca2+  индуцирует активацию  факторов транскрипции, таких как NFAT, JNK1, MEF2, CREB, и в большинстве случаев  является  решающим фактором развития клеток или гибели. В настоящем обзоре рассмотрен механизм  депо-зависимого тока Ca2+  в лимфоцитах

The role of proteins Stim and Orai as molecular components of the store-dependent current Ca2+ in lymphocytes

In the process of evolution of eukaryotes has formatted a highly organized mechanism for maintaining and regulating intracellular calcium homeostasis, which is one of the most important components of cell signaling in all branches of the phylogenetic tree. Intracellular calcium controls numerous physiological processes in the cell. Ca2+ forms signals as their spatial-temporal distribution. The frequency and amplitude of calcium oscillations depends on the signal strength. Calcium signals causing long-term or short-term responses of cells. Mainly, calcium signals in lymphocytes mediate gene expression program initiation that leads to proliferation, differentiation and production of proinflammatory cytokines also activate formation of inflammasome. Therefore, calcium signals mediate immune, and inflammatory response, autoimmune reaction of lymphocytes. The main mechanism of calcium signaling in lymphocytes is store-dependent Ca2+ current. Mobilization of cellular Ca2+ in response to receptor stimulation commonly occurs through release of Ca2+ ions from intracellular Ca2+ stores or influx across the plasma membrane through calcium - selective channels. Calciumselective channels are assembled from two protein families: the Orai proteins which form the ion channel pore, and the stromal interaction molecule (STIM) proteins which function as endoplasmic reticulum calcium sensors and activators of the channel. Stim protein is a transmembrane monomer which is localized at the membrane of the endoplasmic reticulum. This molecule is a sensor Ca2+ in response to emptying store activates calciumselective channels the plasma membrane. These channels express proteins Orai which are tetramers forming inside the channel pore and act as a site Ca2+. Orai binds to Stim. Orai proteins are activated after receiving information from Stim about Store depletion. Thus, the relationship and coordination of Stim and Orai proteins provides store - dependent Ca2+ current and causes cellular functional responses. Increased Ca2+ levels induce the activation of transcription factors such as NFAT, JNK1, MEF2, CREB, and, in most cases, is a crucial factor in the all differentiation or death. In this review, the mechanism of the store-dependent Ca2+ current in lymphocytes is presented

Electrochemical redox transformations of T1 and T2 copper sites in native Trametes hirsuta laccase at gold electrode

Mediatorless, electrochemically driven, redox transformations of T1 (type 1) and T2 copper sites in Trametes hirsuta laccase were studied by cyclic voltammetry and spectroelectrochemical redox titrations using bare gold electrode. DET (direct electron transfer) between the electrode and the enzyme was observed under anaerobic conditions. From analysis of experimental data it is concluded that the T2 copper site is in DET contact with gold. It was found that electron transfer between the gold surface and the T1 copper site progresses through the T2 copper site. From EPR measurements and electrochemical data it is proposed that the redox potential of the T2 site for high-potential ‘blue’ laccase is equal to about 400 mV versus NHE (normal hydrogen electrode) at pH 6.5. The hypothesis that the redox potentials of the T2 copper sites in low- and high-potential laccases/oxidases from totally different sources might be very similar, i.e. approx. 400 mV, is discussed