Y-box protein-1 is actively secreted through a non-classical pathway and acts as an extracellular mitogen

Y-box protein (YB)-1 of the cold-shock protein family functions in gene transcription and RNA processing. Extracellular functions have not been reported, but the YB-1 staining pattern in inflammatory glomerular diseases, without adherence to cell boundaries, suggests an extracellular occurrence. Here, we show the secretion of YB-1 by mesangial and monocytic cells after inflammatory challenges. It should be noted that YB-1 was secreted through a non-classical mode resembling that of the macrophage migration inhibitory factor. YB-1 release requires ATP-binding cassette transporters, and microvesicles protect YB-1 from protease degradation. Two lysine residues in the YB-1 carboxy-terminal domain are crucial for its release, probably because of post-translational modifications. The addition of purified recombinant YB-1 protein to different cell types results in increased DNA synthesis, cell proliferation and migration. Thus, the non-classically secreted YB-1 has extracellular functions and exerts mitogenic as well as promigratory effects in inflammation

Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease

<p>Abstract</p> <p>Background</p> <p>Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases.</p> <p>Methods</p> <p>We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n = 33), patients with non-cancerous, mostly inflammatory diseases (n = 60), hepatocellular carcinoma (HCC; n = 25) and advanced solid tumors (n = 20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation.</p> <p>Results</p> <p>We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients.</p> <p>Conclusions</p> <p>Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should therefore be evaluated in larger prospective studies.</p

Mesangial cell gelatinase A synthesis is attenuated by oscillating hyperbaric pressure.

Glomerular hypertension has been established as a major factor contributing to glomerular scarring. Underlying cellular mechanisms leading to matrix accumulation are largely unknown. The isolated effect of oscillating hyperbaric pressure [OP; P(max) 50 mmHg (1 mmHg=0.133 kPa), P(mean) 24 mmHg, with a fixed oscillation of 60/min] on matrix-degrading protease secretion by rat mesangial cells (MCs) was analysed using a pressure chamber model described previously [Mertens, Espenkott, Venjakob, Heintz, Handt and Sieberth (1998) Hypertension 32, 945-952]. MCs were grown under atmospheric pressure (AP) or a controlled OP, and protease synthesis and gene transcription were analysed. A distinct biphasic cellular response to OP with stimulated gelatinase A protein expression and enzyme activity during the initial 24 h, and subsequent inhibition, was apparent, as shown by gelatin zymography. Gelatinase B activity remained unchanged. The abundance of gelatinase A transcripts, determined by reverse transcriptase-PCR, indicated a concordant regulation of gene transcription. To elucidate underlying regulatory events, reporter constructs were transfected. In these experiments, a recently identified response element, RE-1, conferred a significant stimulatory effect within the initial 4 h of OP. Nuclear protein/RE-1 binding studies revealed additional complexes from 5 min up to 3 h after OP exposure, with intensities dependent on P(max). STAT3 was identified as a component of these novel complexes. Down-regulation of cis-activity after 48 h of OP exposure was not transferred via the proximal 1686 bp of the gelatinase A regulatory sequence. In conclusion, hyperbaric OP elicits time-dependent changes in rat MC gelatinase A gene transcription

За кадры. 1985. № 47 (2540)

На фестиваль / Г. ГригорьеваСлово в дорогу / И. П. ЧучалинГорение / Н. ШатковскаяЗовет трудовое лето! / И. МузейникСпасибо институту / С. АлимоваТребование времени / [беседа с] И. Чуйкин ; [беседа с] А. Киселев ; [беседа с] Т. Петрова ; [беседа с] Т. Кочева ; [беседа с] В. ТаранСемейный проект / Л. КоробейниковаДипломы вручены / Р. ТомиловаДостойное пополнение / Г. Яблонский, А. Фрицлер, В. ВасильевГлядя в завтрашний день / Н. КуцанКрепкие знания / Л. Ларина, М. ПасековНуждается в поддержке / О. ХасановВ пору сенокосную / А. АлександровМеры не помогли / Т. И. ПолуэктоваДвойное дыхание / Р. ГорскаяИтоги спартакиады / А. ВасильевК вершине! / А. ТаенковПрощальный вечер / Г. С. ВоробьеваРазные по жанр