Human cytogenetic consequences of the Chernobyl accident

Schevchenko, V.A.; Akayeva, E. A.; Yeliseyeva, I.M.; Yelisova, T.V.; Yofa, E.L.; Nilova, I.N.; Syomov, Alexander B.; Burkart, W.

doi:10.1016/s0165-1161(96)90226-5

Cited by 19 publications

(9 citation statements)

References 8 publications

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“…The digestion protocol used was based on that of Schevchenko et al with minor variations [24]. Modified porcine trypsin (sequencing grade; Promega, Madison, WI) was added at a final concentration of 16 ng/μl in 25% ACN/50 mM ammonium bicarbonate solution and gels were digested at 37°C for 6 h. The reaction was stopped by adding 0.5% TFA for peptide extraction.…”

Section: Methodsmentioning

confidence: 99%

Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera

et al. 2013

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JAK-STAT signaling through the JAK2V617F mutation is central to the pathogenesis of myeloproliferative neoplasms (MPN). However, other events could precede the JAK2 mutation. The aim of this study is to analyze the phenotypic divergence between polycytemia vera (PV) and essential thrombocytemia (ET) to find novel therapeutics targets by a proteomic and functional approach to identify alternative routes to JAK2 activation. Through 2D-DIGE and mass spectrometry of granulocyte protein from 20 MPN samples, showed differential expression of HSP70 in PV and ET besides other 60 proteins. Immunohistochemistry of 46 MPN bone marrow samples confirmed HSP70 expression. The median of positive granulocytes was 80% in PV (SD 35%) vs. 23% in ET (SD 34.25%). In an ex vivo model KNK437 was used as an inhibition model assay of HSP70, showed dose-dependent inhibition of cell growth and burst formation unit erythroid (BFU-E) in PV and ET, increased apoptosis in the erythroid lineage, and decreased pJAK2 signaling, as well as a specific siRNA for HSP70. These data suggest a key role for HSP70 in proliferation and survival of the erythroid lineage in PV, and may represent a potential therapeutic target in MPN, especially in PV.

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Section: Methodsmentioning

confidence: 99%

Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera

et al. 2013

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“…For re-blotting, the membranes were stripped with stripping buffer (0.2 M NaOH, 0.5 M NaCl) for 10 min and reblotted with antibodies, as specified above. Silver staining was performed, as described before (32).…”

Section: Methodsmentioning

confidence: 99%

The Activity of Hyaluronan Synthase 2 Is Regulated by Dimerization and Ubiquitination

Karousou

Kamiryo

Skandalis

et al. 2010

Journal of Biological Chemistry

114

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Hyaluronan is a component of the extracellular matrix, which affects tissue homeostasis. In this study, we investigated the regulatory mechanisms of one of the hyaluronan-synthesizing enzymes, HAS2. Ectopic expression of Flag-and 6myc-HAS2 in COS-1 cells followed by immunoprecipitation and immunoblotting revealed homodimers; after co-transfection with Flag-HAS3, also heterodimers were seen. Furthermore, the expressed HAS2 was ubiquitinated. We identified one acceptor site for ubiquitin on lysine residue 190. Mutation of this residue led to inactivation of the enzymatic activity of HAS2. Interestingly, K190R-mutated HAS2 formed dimers with wt HAS2 and quenched the activity of wt HAS2, thus demonstrating a functional role of the dimeric configuration.Hyaluronan is abundantly found in tissues throughout the body and has key roles in tissue organization and homeostasis (1). Abnormal accumulation of hyaluronan in tissues and serum is associated with the progression of many diseases, such as inflammatory diseases and cancer (2-5). The biosynthesis of hyaluronan is tightly regulated by growth factors and cytokines as well as other stimuli that promote wound healing, inflammation, or transformation. External regulatory signals, such as platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)-␤, and phorbol 12-myristate 13-acetate (PMA), regulate both the size (6) and amount of the produced hyaluronan (7-14).The hyaluronan-synthesizing enzymes (HAS) 4 were cloned and characterized first in the bacterium Streptococcus pyogenes, and then in mammals, where three different HAS isoforms were characterized, HAS1, HAS2, and HAS3 (15, 16). Studies by us and other laboratories (6, 11) revealed that growth factormediated increase of hyaluronan synthesis is often due to induction of the HAS2 gene in fibroblasts, whereas external signals have been shown to predominantly regulate HAS1 and HAS3 transcripts in synoviocytes and keratinocytes, respectively (12,14,17). In addition to the regulation of HASs at the transcriptional level (6,11,13,14), there is evidence that the activity of HAS isoforms is regulated by phosphorylation by protein kinase C (PKC), protein kinase A (PKA), calcium-dependent protein kinase, and extracellular signal-regulated kinase (10, 18 -20). Prediction from their amino acid sequences suggests that HASs are multi-pass membrane proteins (15) that occur in the plasma membrane, but there are also evidence that much of the HAS enzymes reside at intracellular localizations including perinuclear membrane, endoplasmic reticulum (ER)-Golgi pathway, and endocytic vesicles (21-23).Ubiquitination of proteins affects their stability, activity, interaction with other proteins as well as subcellular localization and trafficking (24, 25). Modification of a protein with K48-linked poly-Ub chains can trigger the proteasomal degradation of the protein. The functional consequences of protein ubiquitination by K63-linked poly-Ub chains include activation of proteins or alteration of their trafficking. Protein modi...

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“…This group consists of about 320,000 people, received 170 mSv in 1986 and 130 mSv in 1987. The frequency of chromosomal aberrations was evaluated in more than 500 liquidators of the Chernobyl accident (Schevchenko et al, 1996). Chromosome aberrations detected in the examined group were represented by dicentrics, paired and nonpaired fragments, acentric rings, and gaps.…”

Section: Occupational Exposures (Liquidators Of the Chernobyl Accident)mentioning

confidence: 99%

“…Chromosome aberrations detected in the examined group were represented by dicentrics, paired and nonpaired fragments, acentric rings, and gaps. Especially in the group of 'sarcophagus' builders, the yields of aberrations varied interindividually and corresponded to equivalent whole body doses of up to about 2 Gy (Schevchenko et al, 1996).…”

Section: Occupational Exposures (Liquidators Of the Chernobyl Accident)mentioning

confidence: 99%

Genetic effects of ionizing radiation – some questions with no answers

Mosse¹

2012

Journal of Environmental Radioactivity

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Human cytogenetic consequences of the Chernobyl accident

Cited by 19 publications

References 8 publications

Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera

Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera

The Activity of Hyaluronan Synthase 2 Is Regulated by Dimerization and Ubiquitination

Genetic effects of ionizing radiation – some questions with no answers

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