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51.
T Yoshida M Ishikawa T Niitsu M Nakazato H Watanabe T Shiraishi A Shiina T Hashimoto N Kanahara T Hasegawa M Enohara A Kimura M Iyo K Hashimoto 《PloS one》2012,7(8):e42676
Background
Meta-analyses have identified serum levels of brain-derived neurotrophic factor (BDNF) as a potential biomarker for major depressive disorder (MDD). However, at the time, commercially available human ELISA kits are unable to distinguish between proBDNF (precursor of BDNF) and mature BDNF because of limited BDNF antibody specificity. In this study, we examined whether serum levels of proBDNF, mature BDNF, and matrix metalloproteinase-9 (MMP-9), which converts proBDNF to mature BDNF, are altered in patients with MDD.Methodology/Principal Findings
Sixty-nine patients with MDD and 78 age- and gender-matched healthy subjects were enrolled. Patients were evaluated using 17 items on the Structured Interview Guide for the Hamilton Depression Rating Scale. Cognitive impairment was evaluated using the CogState battery. Serum levels of proBDNF, mature BDNF, and MMP-9 were measured using ELISA kits. Serum levels of mature BDNF in patients with MDD were significantly lower than those of normal controls. In contrast, there was no difference in the serum levels of proBDNF and MMP-9 between patients and normal controls. While neither proBDNF nor mature BDNF serum levels was associated with clinical variables, there were significant correlations between MMP-9 serum levels and the severity of depression, quality of life scores, and social function scores in patients.Conclusions/Significance
These findings suggest that mature BDNF may serve as a biomarker for MDD, and that MMP-9 may play a role in the pathophysiology of MDD. Further studies using larger sample sizes will be needed to investigate these results. 相似文献52.
53.
Yoshizo Matsuka Takeshi Ono Hirotate Iwase Somsak Mitrirattanakul Kevin S Omoto Ting Cho Yan Yan N Lam Bradley Snyder Igor Spigelman 《Molecular pain》2008,4(1):1-13
Recent advances in pain research provide a clear picture for the molecular mechanisms of acute pain; substantial information concerning plasticity that occurs during neuropathic pain has also become available. The peripheral mechanisms responsible for neuropathic pain are found in the altered gene/protein expression of primary sensory neurons. With damage to peripheral sensory fibers, a variety of changes in pain-related gene expression take place in dorsal root ganglion neurons. These changes, or plasticity, might underlie unique neuropathic pain-specific phenotype modifications – decreased unmyelinated-fiber functions, but increased myelinated A-fiber functions. Another characteristic change is observed in allodynia, the functional change of tactile to nociceptive perception. Throughout a series of studies, using novel nociceptive tests to characterize sensory-fiber or pain modality-specific nociceptive behaviors, it was demonstrated that communication between innocuous and noxious sensory fibers might play a role in allodynia mechanisms. Because neuropathic pain in peripheral and central demyelinating diseases develops as a result of aberrant myelination in experimental animals, demyelination seems to be a key mechanism of plasticity in neuropathic pain. More recently, we discovered that lysophosphatidic acid receptor activation initiates neuropathic pain, as well as possible peripheral mechanims of demyelination after nerve injury. These results lead to further hypotheses of physical communication between innocuous Aβ- and noxious C- or Aδ-fibers to influence the molecular mechanisms of allodynia. 相似文献
54.
Kubo-Murai M Hazeki K Nigorikawa K Omoto T Inoue N Hazeki O 《Journal of biochemistry》2008,143(3):295-302
The activation of interleukin 1 receptor-associated kinase (IRAK)-1 is a key event in the transmission of signals from Toll-like receptors (TLRs). The catalytic activity of the protein kinase is not essential for its ability to activate nuclear factor (NF) kappaB, because transfection of a kinase-dead mutant of IRAK-1 (IRAK-1KD) is able to activate NF-kappaB in HEK293T cells. In the present study, we observed that the effect of IRAK-1KD was impaired by simultaneous expression of IRAK-4. The effect of IRAK-4 was accompanied by the phosphorylation and degradation of IRAK-1KD. Expression of IRAK-4KD instead of IRAK-4 did not cause these events. In IRAK-4-deficient Raw264.7 macrophages that were prepared by introducing short-hairpin RNA probes, the basal level of IRAK-1 was increased markedly. Stimulation of these cells with TLR ligands did not cause the degradation of IRAK-1, which was clearly observed in the parent cells. These results suggested that the expression of IRAK-4 alone is sufficient to cause the degradation of IRAK-1; the autophosphorylation of IRAK-1 is not necessary to terminate the TLR-induced activation of NF-kappaB. IRAK-4 has an ability to induce the degradation of IRAK-1 in addition to its role as an activator of IRAK-1. 相似文献
55.
Immunoglobulin class switch involves a unique recombination event that takes place at the region 5′ to each heavy chain constant region gene during B lymphocyte differentiation. Such regions that are responsible for the class-switch recombination are defined as S regions (Kataoka et al., Proc. Natl. Acad. Sci. USA 77, 919, 1980). We have cloned a rearranged γ2b gene from a mouse myeloma (MPC11) and compared its structure with the germ line counterparts. The rearranged γ2b gene contained the 5′ flanking region of the γ3 gene (Sγ3 region) which are linked to the 5′ flanking region of the γ2b gene (Sγ2b region). We have determined nucleotide sequences surrounding the recombination site of the rearranged and germ line γ2b genes, which include the Sγ2b and Sγ3 regions. Both γ2b and Sγ3 regions comprise tandem repetition of conserved units of 49 bp. Similar 49 bp repeating units are also found in the previously determined sequence of the Sγ1 region in which class-switch recombination took place in MC101 myeloma. The nucleotide sequences of the Sγ1, Sγ2b and Sγ3 repeating units share significant homology with each other. The Sμ region, partial nucleotide sequence of which was previously determined, contains abundant short sequences such as AGCT, TGGG and AGCTGGGG which are shared in common by repeating sequences in Sγ regions. These results suggest that the recombination responsible for class switch from μ to γ or from a γ to another γ, may be facilitated directly or indirectly by homology of repeating sequences in S regions. 相似文献
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58.
PRL family constitutes a unique class of phosphatases associated with metastasis. The phosphatase activity of PRL has been reported to be important for promoting metastasis, and it is inactivated by reversible oxidation of its catalytic cysteine. Here, we show that TRP32 specifically reduces PRL. Reduction of oxidized PRL in cells is inhibited by 2,4-dinitro-1-chlorobenzene, an inhibitor of TRX reductase. In vitro assays for the reduction of PRL show that only TRP32 can potently reduce oxidized PRL, whereas other TRX-related proteins linked to TRX reductase show little or no reducing activity. Indeed, TRP32 knockdown significantly prolongs the H2O2-induced oxidation of PRL. Binding analyses reveal that the unique C-terminal domain of TRP32 is required and sufficient for its direct interaction with PRL. These results suggest that TRP32 maintains the reduced state of PRL and thus regulates the biological function of PRL. 相似文献
59.
Retardation of bone development was observed in the Koshima troop of free ranging Japanese macaques. In the control group,
epiphyseal unions of appendicular long bones generally started to close at about 4 yrs of age and were completed at about
8 or 9 yrs of age. Limb bone unions of the Koshima troop, however, started to close at about 9 yrs of age and completely closed
at about 15 yrs of age. In the epiphyseal unions of trunk and girdle bones, the Koshima troop again showed a retardation of
closure compared with the control group. Until long bones reached their full length, that is, until about 15 yrs of age, their
size was small in the Koshima troop compared with the control group, though the sample size of the Koshima troop was small.
After 15 yrs of age, however, many osteometrical measurements of the Koshima troop were nearly the same as controls. A prolonged
growing duration compensated for the slow growth and allowed them to become as large as controls. This prolongation may be
an adaptation in response to small size during the developmental period.
In some parts of the body, however, Koshima macaques failed to reach the adult size of controls. Males were less likely than
females to reach full size. Causes of the retardation and small size in the Koshima troop are discussed, but they remain open
to further studies. 相似文献