BLOOD FLOW RESTRICTED RESISTANCE TRAINING ATTENUATES MYOSTATIN GENE EXPRESSION IN A PATIENT WITH INCLUSION BODY MYOSITIS

Inclusion body myositis is a rare idiopathic inflammatory myopathy that produces extreme muscle weakness. Blood flow restricted resistance training has been shown to improve muscle strength and muscle hypertrophy in inclusion body myositis. Objective: The aim of this study was to evaluate the effects of a resistance training programme on the expression of genes related to myostatin (MSTN) signalling in one inclusion body myositis patient. Methods: A 65-year-old man with inclusion body myositis underwent blood flow restricted resistance training for 12 weeks. The gene expression of MSTN, follistatin, follistatin-like 3, activin II B receptor, SMAD-7, MyoD, FOXO-3, and MURF-2 was quantified. Results: After 12 weeks of training, a decrease (25%) in MSTN mRNA level was observed, whereas follistatin and follistatin-like 3 gene expression increased by 40% and 70%, respectively. SMAD-7 mRNA level was augmented (20%). FOXO-3 and MURF-2 gene expression increased by 40% and 20%, respectively. No change was observed in activin II B receptor or MyoD gene expression. Conclusions: Blood flow restricted resistance training attenuated MSTN gene expression and also increased expression of myostatin endogenous inhibitors. Blood flow restricted resistance training evoked changes in the expression of genes related to MSTN signalling pathway that could in part explain the muscle hypertrophy previously observed in a patient with inclusion body myositis.     

Mechanisms of lysophosphatidic acid production

Lysophosphatidic acid is one of the most attractive phospholipid mediator with multiple biological functions and is implicated in various human diseases. In the past ten years much has been learned about the physiological roles of LPA through series of studies on LPA actions and its receptors. However, the molecular mechanisms of LPA have been poorly understood. LPA is produced in various conditions both in cells and in biological fluids, where multiple synthetic reactions occur. At least two pathways are postulated. In serum and plasma, LPA is mainly converted from lysophospholipids. By contrast, in platelets and some cancer cells, LPA is converted from phosphatidic acid. In each pathway, at least two phospholipase activities are required: phospholipase A1 (PLA1)/PLA2 plus lysophospholipase D (lysoPLD) activities are involved in the first pathway and phospholipase D (PLD) plus PLA1/PLA2 activities are involved in the second pathway. Now multiple phospholipases are identified that account for PLA1, PLA2, PLD, and lysoPLD activities. In the absence of specific inhibitors and genetically modified animals and individuals, the contribution of each phospholipase to LPA production can not be easily determined. However, apparently certain extracellular phospholipases such as secretory PLA2 (sPLA2-IIA), membrane-associated PA-selective PLA1 (mPA-PLA1), lecithin-cholesterol acyltransferase (LCAT), and lysoPLD are involved in LPA production.     

<Emphasis Type="Italic">N</Emphasis>-Acetylglucosamine 6-<Emphasis Type="Italic">O</Emphasis>-sulfotransferase-2 as a tumor marker for uterine cervical and corpus cancer

N-Acetylglucosamine 6-O-sulfotransferase-2 (GlcNAc6ST2) is ectopically expressed in ovarian mucinous and clear cell adenocarcinoma [Kanoh et al., Glycoconj J 23:453–460, 2006]. Here we studied whether GlcNAc6ST2 protein can be detected in sera from patients with gynecological cancers and could serve as a tumor marker. First, we created a monoclonal antibody and polyclonal antiserum against GlcNAc6ST2. These antibodies were specific for GlcNAc6ST2, as shown by Western blot analysis and immunoprecipitation. Using these antibodies, we constructed a sandwich ELISA method for detecting GlcNAc6ST2 in the serum. GlcNAc6ST2 provided lower positive rates for ovarian cancer than CA125, but higher positive rates for uterine cervical and corpus cancer than SCC antigens and CA125, respectively. A significantly higher percentage of stage I uterine cervical and corpus cancers were positive for GlcNAc6ST2 than for SCC antigens and CA125, respectively. GlcNAc6ST2 could therefore be a good serological marker for detecting early-stage uterine cervical and corpus cancers.     

Identification of the Neuroblastoma-amplified Gene Product as a Component of the Syntaxin 18 Complex Implicated in Golgi-to-Endoplasmic Reticulum Retrograde Transport

Syntaxin 18, a soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) protein implicated in endoplasmic reticulum (ER) membrane fusion, forms a complex with other SNAREs (BNIP1, p31, and Sec22b) and several peripheral membrane components (Sly1, ZW10, and RINT-1). In the present study, we showed that a peripheral membrane protein encoded by the neuroblastoma-amplified gene (NAG) is a subunit of the syntaxin 18 complex. NAG encodes a protein of 2371 amino acids, which exhibits weak similarity to yeast Dsl3p/Sec39p, an 82-kDa component of the complex containing the yeast syntaxin 18 orthologue Ufe1p. Under conditions favoring SNARE complex disassembly, NAG was released from syntaxin 18 but remained in a p31-ZW10-RINT-1 subcomplex. Binding studies showed that the extreme N-terminal region of p31 is responsible for the interaction with NAG and that the N- and the C-terminal regions of NAG interact with p31 and ZW10-RINT-1, respectively. Knockdown of NAG resulted in a reduction in the expression of p31, confirming their intimate relationship. NAG depletion did not substantially affect Golgi morphology and protein export from the ER, but it caused redistribution of Golgi recycling proteins accompanied by a defect in protein glycosylation. These results together suggest that NAG links between p31 and ZW10-RINT-1 and is involved in Golgi-to-ER transport.     

Phylogeographical patterns of a generalist acorn weevil: insight into the biogeographical history of broadleaved deciduous and evergreen forests

Background  

Climatic changes during glacial periods have had a major influence on the recent evolutionary history of living organisms, even in temperate forests on islands, where the land was not covered with ice sheets. We investigated the phylogeographical patterns of the weevil Curculio sikkimensis (Curculionidae), a generalist seed predator of Fagaceae plants living in both deciduous oak and evergreen forests of Japan. Its genetic structure was compared to that of another host-specific seed predator, C. hilgendorfi, inhabiting only evergreen forests.