The mechanism of low-concentration sodium nitroprusside-mediated protection of chondrocyte death

Sodium nitroprusside (SNP), a widely used nitric oxide donor, has recently been shown to mediate chondrocyte apoptosis by generating reactive oxygen species, whereas more potent nitric oxide donors do not induce chondrocyte apoptosis. The present study was performed to investigate the protective effect of a low concentration of SNP upon the cytotoxicity of chondrocytes to higher concentrations of SNP, and to elucidate the underlying mechanism. Human osteoarthritis chondrocytes were cultured as monolayers, and first-passage cells were used for the experiments. Chondrocyte death induced by 1 mM SNP was completely inhibited by pretreating with 0.1 mM SNP. This protective effect of SNP was replicated by the guanosine-3',5'κ-cyclic monophosphate analog, DBcGMP. Protection from chondrocyte death conferred by 0.1 mM SNP was mediated by heme oxygenase 1 (HO-1), as was revealed by the increased expression of HO-1 in 0.1 mM SNP pretreated chondrocytes and by the reversal of this protective effect by the HO-1 inhibitor, zinc protoporphyrin. SNP-mediated chondrocyte protection correlated with the downregulation of both extracellular signal-regulated protein kinase 1/2 and p38 kinase activation. SNP at 0.1 mM induced significant NF-κB activation as revealed by electrophoretic mobility shift assays, and the inhibition of NF-κB by MG132 or Bay 11-7082 nullified 0.1 mM SNP-mediated chondrocyte protection. The upregulation of p53 and the downregulation of Bcl-(XL )and Mcl-1 by 1 mM SNP were reversed by 0.1 mM SNP pretreatment at the protein level by western blotting. Our study shows that priming with 0.1 mM SNP confers complete protection against cell death induced by 1 mM SNP in human articular chondrocytes. This protective effect was found to be correlated with the upregulation of both HO-1 and NF-κB and with the concomitant downregulation of both extracellular signal-regulated protein kinase 1/2 and p38 activation

Semiconductor integrated circuit chip, multilayer chip capacitor and semiconductor integrated circuit chip package

Disclosed are a semiconductor integrated circuit chip, a multilayer chip capacitor, and a semiconductor integrated circuit chip package. The semiconductor integrated circuit chip includes a semiconductor integrated circuit chip body, an input/output terminal disposed on the outside of the semiconductor integrated circuit chip body, and a decoupling capacitor disposed at a side face of the semiconductor integrated circuit chip body and electrically connected to the input/output terminal. The semiconductor integrated circuit chip cab be obtained, which can maintain an impedance of a power distribution network below a target impedance in a wide frequency range, particularly at a high frequency, by minimizing an inductance between a decoupling capacitor and a semiconductor integrated circuit chip

Transmembrane topology and oligomeric nature of an astrocytic membrane protein, MLC1

MLC1 is a membrane protein mainly expressed in astrocytes, and genetic mutations lead to the development of a leukodystrophy, megalencephalic leukoencephalopathy with subcortical cysts disease. Currently, the biochemical properties of the MLC1 protein are largely unknown. In this study, we aimed to characterize the transmembrane (TM) topology and oligomeric nature of the MLC1 protein. Systematic immunofluorescence staining data revealed that the MLC1 protein has eight TM domains and that both the N- and C-terminus face the cytoplasm. We found that MLC1 can be purified as an oligomer and could form a trimeric complex in both detergent micelles and reconstituted proteoliposomes. Additionally, a single-molecule photobleaching experiment showed that MLC1 protein complexes could consist of three MLC1 monomers in the reconstituted proteoliposomes. These results can provide a basis for both the high-resolution structural determination and functional characterization of the MLC1 protein.1

Possible Mechanism on Enhanced Blood Compatibility, Biostability, and Anticalcification of Sulfonated Polyethyleneoxide-Grafted Polyurethane

To investigate the correlation between blood compatibility and biostability as well as the calcification-resistance of polymers, the surface of polyurethane (PU) was grafted with hydrophilic polyethyleneoxide (PEO), and further negatively charged sulfonate groups (S03) to produce PU-PEOIOOO and PU-PEOIOOOS03, respectively. PEO-S03 grafted PU surface showed great smoothness and high hydrophilicity. PU-PEOIOOO-S03 was much more blood compatible than untreated PU and PU-PEOlOOO from the results of in vitro platelet adhesion test and blood clotting times and ex vivo occlusion times. After 6 months implantation in rats, the degree of surface cracking and calcification on explanted PUs was decreased in the following order: PU ) PU-PEOIOOO ) PU-PEOlOOO-S03, meaning that PU-PEOlOOO-S03 is most promising as a biostable and calcification-resistant polymer. It is suggested that the more blood compatible modified PUs are, the more biostable and calcification-resistant. Such superior blood compatibility, biostability, and anticalcification of PU-PEOlOO 0-S03 might be attributed to the synergistic effect of nonadhesive and mobile PEO and negative sulfonate acid groups. Therefore, surface-modified PU-PEO-S03is expected to be useful for blood/tissue contacting biomedical material