Hepatocyte growth factor (HGF), a potent mitogen for mature hepatocytes, possesses mitogenic and morphogenic activities for renal epithelial cells. To examine the renotropic function of HGF, we investigated the expression of HGF mRNA and HGF activity in the rat kidney after acute renal failure. When acute renal failure was induced by ischemia or by HgCl2 administration, a DNA synthesis occurred predominantly in the renal tubular cells located in the outer medulla with a peak at 48 h after the treatments. In both renal injuries, HGF mRNA in the kidney increased markedly, reaching a maximum 6 to 12 h after the treatments. HGF activity in the kidney also increased to three- to fourfold higher level than the normal level at 12 h after ischemic treatment or HgCl2 administration. In situ hybridization and immunohistochemical analysis indicated that both HGF mRNA and HGF protein were expressed in renal interstitial cells, presumably endothelial cells and macrophages, but not in tubular epithelial cells. In addition, HGF activity in the plasma of rats with renal ischemia or HgCl2 administration rapidly increased, reaching a maximum at 6 h after the treatment. One week after these injuries, HGF mRNA and HGF activity reverted to normal levels, and renal tubular cell regeneration ceased. Moreover, intravenous injection of human recombinant HGF into mice with acute renal failure caused by HgCl2 administration stimulated DNA synthesis of renal tubular cells in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

Unconventional mRNA splicing on the endoplasmic reticulum (ER) membrane is the sole conserved mechanism in eukaryotes to transmit information regarding misfolded protein accumulation to the nucleus to activate the stress response. In metazoans, the unspliced form of X-box-binding protein 1 (XBP1u) mRNA is recruited to membranes as a ribosome nascent chain (RNC) complex for efficient splicing. We previously reported that both hydrophobic (HR2) and translational pausing regions of XBP1u are important for the recruitment of its own mRNA to membranes. However, its precise location and the molecular mechanism of translocation are unclear. We show that XBP1u-RNC is specifically recruited to the ER membrane in an HR2-and translational pausing-dependent manner by immunostaining, fluorescent recovery after photobleaching, and biochemical analyses. Notably, translational pausing during XBP1u synthesis is indispensable for the recognition of HR2 by the signal recognition particle (SRP), resulting in efficient ER-specific targeting of the complex, similar to secretory protein targeting to the ER. On the ER, the XBP1u nascent chain is transferred from the SRP to the translocon; however, it cannot pass through the translocon or insert into the membrane. Therefore, our results support a noncanonical mechanism by which mRNA substrates are recruited to the ER for unconventional splicing. and subsequent protein folding are associated with a number of diseases. Accordingly, a detailed understanding of the mechanisms that mediate these complex processes is necessary. In eukaryotes, secretory proteins are initially translated by cytosolic ribosomes. When the N-terminal signal peptide reaches outside of the peptide exit channel in the ribosome, the ribosome nascent chain (RNC) complex is recognized by the signal recognition particle (SRP) and peptide elongation is slowed (1-5). This SRP-RNC complex is then recruited to the ER via the affinity between SRP and SRP receptor (SR) that exists in the ER membrane (2, 3). The RNC complex is then delivered to the polypeptide channel in the ER (i.e., the Sec61 translocon) (6). SRP is released from the RNC, which cancels the slowed-down elongation. As a result, the ER-targeted ribosome cotranslationally translocates its synthesizing polypeptide into the luminal space of the ER. The translocated protein is folded into its native 3D structure with the help of molecular chaperones and folding enzymes (7). The folded proteins are sorted to their final destinations to exert their functions.The burden of new proteins entering the ER varies widely among conditions, such as cell differentiation, environmental conditions, and the physiological state of the cell (8, 9). In addition, the folding capacity in the ER is easily compromised by many stressful conditions, including glucose starvation, virus infection, and perturbations in the Ca 2+ concentration. Therefore, it is necessary for cells to manage the imbalance between the load of newly entering proteins and the folding capacity in the ER, and this i...

No need for nobles: The copper‐based metal–organic framework material N,N′‐bis(2‐hydroxyethyl)dithiooxamidatocopper(II) (see picture, Cu pink, N blue, S yellow, O red, C gray, H white) is an active catalyst for ethanol electrooxidation. The performance of this noble‐metal‐free material is comparable to those of some reported Pt‐based catalysts.

In a family of catena-μ-N,N′-disubstituted dithiooxamidocopper(II) complexes which have been assumed as two-dimensional coordination polymers, one complex with HOC2H4- substituents is an electronic conductor as well as others, and also a protonic conductor uniquely. The latter property was proved both by spectroscopic detection of the hydrogen molecules evolved from d.c. electrolysis of pressed pellets of the powder specimen and by observation of the anomalous increase (three orders of magnitude) of the electric conductivity as an effect of 103 Pa of H2O or D2O vapor on the dehydrated specimen in an evacuated conductivity cell. A novel conduction mechanism was suggested for such a solid system with both conjugated double bonds and extended hydrogen bonds.