No abstract available

[en] Highlights: • Oxidative stress is involved in CoCl₂-induced hypoxic cytotoxicity in HaCaT cells. • CoCl₂ and physical hypoxia activate NRF2-mediated antioxidant response in HaCaT cells. • NRF2 silencing sensitizes HaCaT cells to CoCl₂ and physical hypoxia-induced toxicity. • KEAP1-KD HaCaT cells show elevated NRF2 protein expression and activity. • KEAP1-KD HaCaT cells become resistant to CoCl₂ cytotoxicity. Hypoxia is a key pathological process involved in many cutaneous diseases. Nuclear factor E2-related factor 2 (NRF2) is a central regulator of antioxidant response element (ARE)-dependent transcription and plays a pivotal role in the cellular adaptive response to oxidative stress. Kelch-like ECH-associated protein 1 (KEAP1) is a cullin-3-adapter protein that represses the activity of NRF2 by mediating its ubiquitination and degradation. In the present study, we examined the role of NRF2 signaling pathway in the cytotoxicity induced by cobalt chloride(CoCl₂), a hypoxia-mimicking agent, in human keratinocyte HaCaT cells with stable knockdown of NRF2 (NRF2-KD) and KEAP1 (KEAP1-KD). Acute CoCl₂ exposure markedly increased the levels of intracellular reactive oxygen species (ROS), and resulted in hypoxic damage and cytotoxicity of HaCaT cells. Stable knockdown of NRF2 dramatically reduced the expression of many antioxidant enzymes and sensitized the cells to acute CoCl₂-induced oxidative stress and cytotoxicity. In contrast, KEAP1-KD cells observably enhanced the activity of NRF2 and ARE-regulated genes and led to a significant resistance to CoCl₂-induced cellular damage. In addition, pretreatment of HaCaT cells with tert-butylhydroquinone, a well-known NRF2 activator, protected HaCaT cells from CoCl₂-induced cellular injury in a NRF2-dependent fashion. Likewise, physical hypoxia-induced cytotoxicity could be significantly ameliorated through NRF2 signaling pathway in HaCaT cells. Together, our results suggest that NRF2 signaling pathway is involved in antioxidant response triggered by CoCl₂-induced oxidative stress and could protect human keratinocytes against acute CoCl₂ -induced hypoxic cytotoxicity.

No abstract available

[en] Highlights: • MALAT1 was up-regulated in CPCs in hypoxia conditions. • MALAT1 suppression inhibited CPCs proliferation and migration after hypoxia-inducing stimuli. • MALAT1 modulated CPCs proliferation and migration through MALAT1/miR-125/JMJD6 axis under hypoxia conditions. The death of cardiomyocytes after myocardial infarction (MI) often leads to ventricular remodeling as well as heart failure (HF). The cardiac progenitor cells (CPCs) have the ability to regenerate functional heart muscle in patients after MI, which provides a promising method for MI-induced HF therapy. However, to date, CPCs can easily lose their proliferation ability in the infarcted myocardium. Therefore, exploring the mechanism for CPC proliferation is essential for CPC-based therapy in MI-induced HF. A previous study indicated that a hypoxic environment is essential for CPC proliferation, but the mechanism is not yet clear. In this work, we discovered that CoCl₂-induced hypoxia can promote CPC proliferation and migration. Additionally, long non-coding RNA MALAT1 expression was significantly up-regulated in the CoCl₂-induced hypoxia CPC model. MALAT1 suppression inhibited CPC proliferation and migration under hypoxic conditions. In addition, MALAT1 acted as a sponge for miR-125. The miR-125 inhibitor restored the proliferation and migration potentials of CPCs after a MALAT1 knockdown in hypoxia. A further study demonstrated that JMJD6 was a target of miR-125 whose expression was negatively regulated by miR-125. JMJD6 knockdown blocked miR-125 inhibitor's protective effect on CPC function in hypoxia. Ultimately, our finding demonstrated that MALAT1 can modulate CPC proliferation and migration potential through the miR-125/JMJD6 axis in hypoxia. Our finding provided a new regulatory mechanism for CPC proliferation in hypoxia, which provided a new target for MI-induced HF therapy.

[en] We have found that vic-dibromides treated with CoCl₂·6H₂O/indium system in methanol are efficiently converted into the corresponding alkenes in high yields under mild conditions. Although the scope and limitations of this method have not been fully established, it is expected to be a useful and efficient alternative to the existing methods for the debromination of vic-dibromides. There is always considerable interest in the search for more efficient and selective procedures for the debromination of vic-dibromides. The reduction of CoCl₂ to low-valent cobalt species and the synthetic utility of such species are well documented in the literature. Generally, reducing agents, such as zinc and magnesium, are used for the reduction of CoCl₂. Because indium and zinc closely resemble each other in several aspects, including first ionization, we considered that a combination of CoCl₂·6H₂O with indium could facilitate the reductive debromination of vic-dibromides under mild conditions. As in the case of zinc, the reduction potential of indium is not highly negative (In: E^o, In⁺³/In = -0.345 V; Zn: E^o, Zn:⁺²/Zn = -0.763 V): thus, indium is not sensitive to water and does not form oxides readily in air. In recent years, indium metal has been the subject of active interest because of its unique properties such as low toxicity and high stability in water and air compared to other metals. In connection with our interest in exploring the utility of low-valent metal reagents for organic transformations, we herein wish to report an efficient and chemoselective method for the debromination of vic-dibromides to alkenes using CoCl₂·6H₂O/indium system at room temperature

[en] The preparation of L-thyroxine labelled with ⁵⁷cobalt for use as a second tracer in dual radioimmunoassay techniques for different biological molecules is described. The labelling procedure was monitored by paper chromatography and polyacrylamide gel electrophoresis; a yield of 42±10% (mean ±1 SD) was achieved in a total of 39 conjugation reactions. The method was optimized in terms of pH, reaction completion time, reactant concentration, and solubility of the tracer. A radioimmunoassay for thyroxine in human serum was developed utilizing this tracer, and this compared favorably with an established technique in which ¹²⁵iodine was used as the tracer. 16 refs.; 6 figs.; 1 table

[en] In this study, we developed an optical-fiber sensor using cobalt chloride solution to monitor temperature in real-time between long distance points unaffected by the electro-magnetic wave and the vibration. Cobalt chloride solutions were made using 10% water and 90% ethanol (v/v) solution. The transmittance of these solutions was analyzed on 655 nm using UV-Visible spectrometer regarding temperature change. Also 30.8 mM cobalt chloride solution was gelled by dissolving polyvinyl butyral and the transmittance of this was analyzed on 655 nm regarding temperature change. The results of transmittance and optical power measurement showed decrease of both transmittance and optical power with increase of temperature from 66.8% and 149.5 nW at 25 .deg. C to 7.1% and 48 nW at 70 .deg. C, respectively. These results support the possibility of gelled cobalt chloride/polyvinyl butyral as an optical-fiber sensor to monitor temperature change

[en] Class I histone deacetylases (HDACs) have been reported to be overexpressed in clear cell renal cell carcinoma (ccRCC), whereas the expression of class II HDACs is unknown. Four isogenic cell lines C2/C2VHL and 786-O/786-OVHL with differential VHL expression are used in our studies. Cobalt chloride is used to mimic hypoxia in vitro. HIF-2α knockdowns in C2 and 786-O cells is used to evaluate the effect on HDAC 1 expression and activity. Invasion and migration assays are used to investigate the role of HDAC 1 and HDAC 6 expression in ccRCC cells. Comparisons are made between experimental groups using the paired T-test, the two-sample Student’s T-test or one-way ANOVA, as appropriate. ccRCC and the TCGA dataset are used to observe the clinical correlation between HDAC 1 and HDAC 6 overexpression and overall and progression free survival. Our analysis of tumor and matched non-tumor tissues from radical nephrectomies showed overexpression of class I and II HDACs (HDAC6 only in a subset of patients). In vitro, both HDAC1 and HDAC6 over-expression increased cell invasion and motility, respectively, in ccRCC cells. HDAC1 regulated invasiveness by increasing matrix metalloproteinase (MMP) expression. Furthermore, hypoxia stimulation in VHL-reconstituted cell lines increased HIF isoforms and HDAC1 expression. Presence of hypoxia response elements in the HDAC1 promoter along with chromatin immunoprecipitation data suggests that HIF-2α is a transcriptional regulator of HDAC1 gene. Conversely, HDAC6 and estrogen receptor alpha (ERα) were co-localized in cytoplasm of ccRCC cells and HDAC6 enhanced cell motility by decreasing acetylated α-tubulin expression, and this biological effect was attenuated by either biochemical or pharmacological inhibition. Finally, analysis of human ccRCC specimens revealed positive correlation between HIF isoforms and HDAC. HDAC1 mRNA upregulation was associated with worse overall survival in the TCGA dataset. Taking together, these results suggest that HDAC1 and HDAC6 may play a role in ccRCC biology and could represent rational therapeutic targets. The online version of this article (doi:10.1186/s12885-016-2604-7) contains supplementary material, which is available to authorized users

[en] The mammalian stress protein Hsp105α protects cells from stress conditions. Several studies have indicated that Hsp105α is overexpressed in many types of solid tumors, which contain hypoxic microenvironments. However, the role of Hsp105α in hypoxic tumors remains largely unknown. We herein demonstrated the involvement of Hsp105α in HIF-1 functions induced by the hypoxia-mimetic agent CoCl_2. While Hsp105α is mainly localized in the cytoplasm under normal conditions, a treatment with CoCl_2 induces the nuclear localization of Hsp105α, which correlated with HIF-1α expression levels. The overexpression of degradation-resistant HIF-1α enhances the nuclear localization of Hsp105α without the CoCl_2 treatment. The CoCl_2-dependent transcriptional activation of HIF-1, which is measured using a reporter gene containing a HIF-responsive element, is reduced by the knockdown of Hsp105α. Furthermore, the CoCl_2-induced accumulation of HIF-1α is enhanced by heat shock, which results in the nuclear localization of Hsp105, and is suppressed by the knockdown of Hsp105. Hsp105 associates with HIF-1α in CoCl_2-treated cells. These results suggest that Hsp105α plays an important role in the functions of HIF-1 under hypoxic conditions, in which Hsp105α enhances the accumulation and transcriptional activity of HIF-1 through the HIF-1α-mediated nuclear localization of Hsp105α. - Highlights: • Hsp105α is required for the CoCl_2-induced transcriptional activation and accumulation of HIF-1. • Hsp105α localizes to the nucleus and interacts with HIF-1α in CoCl_2-treated cells. • Hsp105 enhances the CoCl_2-induced accumulation of HIF-1α under heat shock conditions.

[en] The preparation of an oligomeric complex obtained from the reaction of 1,1'-bis(octadecyl)-2,2'-benzimidazole and CoCl₂ is reported. This oligomer has been characterized by UV-visible spectroscopy, FT-IR and ¹H-RMN. Elemental analysis does not yield a definite relationship between the cobalt and the ligand. The oligomeric complex undergoes decomposition when heating according to DSC analysis. (author)