Секретируемый белок YB-1 и его прогностическая значимость

The multifunctional protein YB-1 in prokaryotes and eukaryotes participates in various processes, among others performing the functions  of a regulator of transcription and translation of many genes. Intracellular localization and expression of YB-1 is an acknowledged prognostic marker for certain malignant tumors. However, it has recently become clear that YB-1 can be released from cells and present in body fluids, including inside vesicles. The review collected data on the secretion YB-1 (sYB-1) content in blood serum from patients with inflammatory diseases and various tumors. There is analyzed the influence of sYB-1 on normal and tumor cells. Data are presented that show that intracellular YB-1 and sYB-1 affect cells differently. The prognostic significance of sYB-1 and its form YB-1/p18 in malignant neoplasms is discussed.Многофункциональный белок YB-1 (Y box-binding protein 1) в клетках прокариот и эукариот участвует в различных процессах, среди других выполняя функции регулятора транскрипции и трансляции многих генов. Внутриклеточная локализация и экспрессия YB-1 является признанным прогностическим маркером для некоторых злокачественных новообразований. Однако относительно недавно стало понятно, что YB-1 может выделятся из клеток и присутствует в жидкостях организма, в том числе находясь внутри везикул. В обзоре собраны данные относительно содержания секретируемого YB-1 (сYB-1) в сыворотке крови у больных с воспалительными заболеваниями и различными опухолями. Изучается влияние сYB-1 на нормальные и опухолевые клетки. Рассматриваются данные, показывающие, что внутриклеточный YB-1 и сYB-1 по-разному влияют на клетки. Обсуждается прогностическая значимость сYB-1 и его формы YB-1 / р18 при злокачественных новообразованиях

Secreted protein YB-1 and its prognostic significance

The multifunctional protein YB-1 in prokaryotes and eukaryotes participates in various processes, among others performing the functions  of a regulator of transcription and translation of many genes. Intracellular localization and expression of YB-1 is an acknowledged prognostic marker for certain malignant tumors. However, it has recently become clear that YB-1 can be released from cells and present in body fluids, including inside vesicles. The review collected data on the secretion YB-1 (sYB-1) content in blood serum from patients with inflammatory diseases and various tumors. There is analyzed the influence of sYB-1 on normal and tumor cells. Data are presented that show that intracellular YB-1 and sYB-1 affect cells differently. The prognostic significance of sYB-1 and its form YB-1/p18 in malignant neoplasms is discussed

Disturbed Ca(2+) signaling and apoptosis of medium spiny neurons in Huntington's disease

Huntington's disease (HD) is caused by polyglutamine expansion (exp) in huntingtin. Here, we used a yeast artificial chromosome (YAC) transgenic mouse model of HD to investigate the connection between disturbed calcium (Ca(2+)) signaling and apoptosis of HD medium spiny neurons (MSN). Repetitive application of glutamate elevates cytosolic Ca(2+) levels in MSN from the YAC128 mouse but not in MSN from the wild-type or control YAC18 mouse. Application of glutamate results in apoptosis of YAC128 MSN but not wild-type or YAC18 MSN. Analysis of glutamate-induced apoptosis of the YAC128 MSN revealed that (i) actions of glutamate are mediated by mGluR1/5 and NR2B glutamate receptors; (ii) membrane-permeable inositol 1,4,5-trisphosphate receptor blockers 2-APB and Enoxaparin (Lovenox) are neuroprotective; (iii) apoptosis involves the intrinsic pathway mediated by release of mitochondrial cytochrome c and activation of caspases 9 and 3; (iv) apoptosis requires mitochondrial Ca(2+) overload and can be prevented by the mitochondrial Ca(2+) uniporter blocker Ruthenium 360; and (v) apoptosis involves opening of mitochondrial permeability transition pore (MPTP) and can be prevented by MPTP blockers such as bongkrekic acid, Nortriptyline, Desipramine, Trifluoperazine, and Maprotiline. These findings describe a pathway directly linking disturbed Ca(2+) signaling and degeneration of MSN in the caudate nucleus in HD. These findings also suggest that Ca(2+) and MPTP blockers may have a therapeutic potential for treatment of HD

Minocycline inhibits caspase-independent and -dependent mitochondrial cell death pathways in models of Huntington's disease

Minocycline is broadly protective in neurologic disease models featuring cell death and is being evaluated in clinical trials. We previously demonstrated that minocycline-mediated protection against caspase-dependent cell death related to its ability to prevent mitochondrial cytochrome c release. These results do not explain whether or how minocycline protects against caspase-independent cell death. Furthermore, there is no information on whether Smac/Diablo or apoptosis-inducing factor might play a role in chronic neurodegeneration. In a striatal cell model of Huntington's disease and in R6/2 mice, we demonstrate the association of cell death/disease progression with the recruitment of mitochondrial caspase-independent (apoptosis-inducing factor) and caspase-dependent (Smac/Diablo and cytochrome c) triggers. We show that minocycline is a drug that directly inhibits both caspase-independent and -dependent mitochondrial cell death pathways. Furthermore, this report demonstrates recruitment of Smac/Diablo and apoptosis-inducing factor in chronic neurodegeneration. Our results further delineate the mechanism by which minocycline mediates its remarkably broad neuroprotective effects