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The exposure to UVA (320–400 nm) irradiation is a major threat to human skin concerning photoaging and carcinogenesis. It has been shown that UVA irradiation can induce reactive oxygen species (ROS) and DNA mutations, such as 8-hydroxydeoxyguanosine. Furthermore, UVA induces the expression of photoaging-associated matrix metalloproteases (MMPs), especially of matrix metalloprotease 1 (MMP 1) and matrix metalloprotease 3 (MMP 3). In addition to this, it was recently shown that UVA-induced ROS also increase glucose metabolism of melanoma cells, however, the influence of UVA on the glucose metabolism of non-malignant cells of the human skin has, so far, not been investigated in detail. Here, we investigated the UVA-induced changes in glucose metabolism and the functional relevance of these changes in primary fibroblasts—normal non-malignant cells of the skin. These cells showed an UVA-induced enhanced glucose consumption and lactate production and changes in pyruvate production. As it has been proposed that pyruvate could have antioxidant properties we tested the functional relevance of pyruvate as protective agent against UVA-induced ROS. Our initial experiments support earlier publications, demonstrating that pyruvate treated with H2O2 is non-enzymatically transformed to acetate. Furthermore, we show that this decarboxylation of pyruvate to acetate also occurs upon UVA irradiation. In addition to this, we could show that in fibroblasts pyruvate has antioxidant properties as enhanced levels of pyruvate protect cells from UVA-induced ROS and partially from a DNA mutation by the modified base 8-hydroxydeoxyguanosine. Furthermore, we describe for the first time, that the interaction of UVA with pyruvate is relevant for the regulation of photoaging-associated MMP 1 and MMP 3 expression. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article on sensitization of acute lymphoblastic leukemia cells to glucocorticoid-induced apoptosis by low doses of 2-deoxy-glucose published in the August 6, 2009 issue.

Many studies in recent years suggest that schizophrenia is a synaptic disease that crucially involves a hypofunction of N-methyl-D-aspartate receptor-mediated signaling. However, at present it is unclear how these pathological processes are reflected in the protein content of the synapse. We have employed two-dimensional gel electrophoresis in conjunction with mass spectrometry to characterize and compare the synaptic proteomes of the human left dorsolateral prefrontal cortex in chronic schizophrenia and of the cerebral cortex of rats treated subchronically with ketamine. We found consistent changes in the synaptic proteomes of human schizophrenics and in rats with induced ketamine psychosis compared to controls. However, commonly regulated proteins between both groups were very limited and only prohibitin was found upregulated in both chronic schizophrenia and the rat ketamine model. Prohibitin, however, could be a new potential marker for the synaptic pathology of schizophrenia and might be causally involved in the disease process.Molecular Psychiatry (2008) 13, 878–896; doi:10.1038/mp.2008.60; published online 27 May 2008 [ABSTRACT FROM AUTHOR]

The lysozyme (LZM) gene provides a very useful model for studies of phagocyte maturation, because its protein synthesis is increased during myelopoiesis and thus most abundant in terminally differentiated and activated phagoyctes. LZM gene expression and DNA methylation were examined in various normal and transformed hematopoietic cells. Two shifts toward LZM gene demethylation coincided with upregulation of expression: activation of expression in myeloid precursor cells was associated with significant demethylation at a CpG dinucleotide within an Alu repeat in the 5' flanking region; high-level expression in different types of mature phagocytic cells was associated with complete demethylation at two additional, intragenic CpG sites contained in Alu sequences. The possibility that methylation changes occurring within the 5' region of the human lysozyme gene could be involved in the transcription of this gene is discussed, as well as a possible role for demethylation in the maintenance of distinct maturation stages during phagocyte development. [ABSTRACT FROM AUTHOR]

Cells of the macrophage lineage are a major source of various cytokines and hematopoietic growth factors. With regard to the growth factors acting on cells of their own lineage, macrophage colony-stimulating factor (M-CSF) has been proven to be secreted by monocytes (MO) and macrophages (MAC), whereas the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by human MO/MAC is under debate. Here we report that in elutriation-purified MO, as well as in MAC derived from cultured MO, GM-CSF m-RNA was regularly induced by LPS. In MO the GM-CSF message was still detectable 18 h after stimulation under serum-free conditions, but in contrast was already lost at this time point in MAC. Secreted GM-CSF protein was detected in the culture medium using a sandwich ELISA. Furthermore, a factor-dependent cell line (M-07) was used for a biological assay. Here, a neutralizing anti GM-CSF antibody specifically blocked the proliferation-inducing activity of MO/MAC supernatants. Whereas only small amounts of GM-CSF were detected in MO, its secretion increased severalfold upon MO-to-MAC differentiation in vitro. A similar increase upon in vitro maturation of MO was observed for the production of granulocyte colony-stimulating factor. The highest amounts of GM-CSF (up to 2.8 ng/10(6) cells) were produced by MAC that had been derived from MO cultured under serum-free conditions in the presence of 0.5 mg/ml albumin as the only medium supplement. [ABSTRACT FROM AUTHOR]

Presents the findings of a study on the variations in 1a,25-dihydroxyvitamin D3 and 25-dihydroxyvitamin D3 serum levels during allogenic bone marrow transplantation (BMT). Effects of active form of 1.25(OH)2 D3 in BMT; Measurement of both vitamins in consecutive serum samples of patients before and after allogenic BMT; Observation of marked decline in serum levels; Superior effects on bone density and modulation of graft-versus-host disease with supplementation of patients with 1,25(OH)2 D3 analogs or 25(OH) D3.