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1.  Treatment of Moyamoya Syndrome Associated with Systemic Lupus Erythematosus and Hypothyroidism in an Adult by Encephaloduroarteriosynangiosis: A Case Report 
Case Reports in Medicine  2012;2012:120867.
A 54-year-old woman presented to our hospital with progressive motor weakness of the right arm. She had a medical history of systemic lupus erythematosus (SLE) and hypothyroidism. Magnetic resonance imaging indicated a watershed infarction of the left hemisphere. Cervical echogram indicated severe stenosis of the internal carotid artery (ICA) without wall thickening. Cerebral angiography indicated left ICA occlusion, development of unilateral moyamoya vessels, and leptomeningeal anastomosis. Encephaloduroarteriosynangiosis (EDAS) was performed after cerebral 99mTechnetium-ethyl-cysteinate-dimer single-photon emission computed tomography indicated a decreased cerebral blood flow, diminished cerebrovascular perfusion reserve. Motor weakness finally disappeared 6 months after surgery. Moyamoya syndrome is a rare complication of both SLE and hypothyroidism, and the surgical indication remains controversial. By evaluating the decreased cerebral perfusion reserve capacity and the existence of leptomeningeal anastomosis, EDAS could be an efficient method for the treatment of moyamoya syndrome associated with SLE and hypothyroidism.
PMCID: PMC3432552  PMID: 22966233
2.  Acidification of the Golgi apparatus is indispensable for maturation but not for cell surface delivery of Ret 
Journal of neurochemistry  2010;115(3):606-613.
We examined the effect of concanamycin A and bafilomycin A1, inhibitors of the vacuolar proton-ATPase, on maturation and expression of Ret, a tyrosine kinase receptor for glial cell line-derived neurotrophic factor. Ret appeared as 150- and 170-kDa bands on sodium dodecyl sulfate–polyacrylamide gel electrophoresis gels and both forms were sensitive to peptide-N-glycosidase F. Western and immunocytochemical analyses revealed that the 150-kDa immature form of Ret accumulated in the Golgi apparatus upon treatment with vacuolar proton-ATPase inhibitors, whereas, the 170-kDa mature form of Ret was dramatically decreased. The result suggests that glycosylation of Ret during the conversion from immature forms to mature forms is pH sensitive, and is likely initiated in the acidic trans-Golgi apparatus. In contrast, glycosylation of nascent receptors to become immature receptors appeared to be pH insensitive, and are likely to take place in the endoplasmic reticulum. The immature form of Ret was present in the plasma membrane when the cells were treated with the vacuolar proton-ATPase inhibitors. In conclusion, the acidification of the Golgi apparatus is crucial for maturation of Ret but not indispensable for trafficking of receptors to the membrane.
PMCID: PMC3415695  PMID: 20796177
bafilomycin A1; concanamycin A; EGFR; PC12 cells; Ret
3.  Characterization of 3'-untranslated region of the mouse GDNF gene 
Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for many cell types, and its expression is widespread both within and outside of the nervous system. The regulation of GDNF expression has been extensively investigated but is not fully understood.
Using a luciferase reporter assay, we identified the role of the 3'-untranslated region (3'-UTR) of the mouse GDNF gene in the regulation of gene expression. We focused on a well-conserved A- and T-rich region (approximately 200 bp in length), which is located approximately 1000 bp downstream of the stop codon in exon 4 of the gene and contains three typical AU-rich elements (AREs), AUUUA. Interestingly, these AREs are well conserved in several GDNF genes. By testing reporter constructs containing various regions and lengths of the 3'-UTR fused to the end of the luciferase gene, we demonstrated that the ARE-induced decrease in luciferase activity correlates with the attenuation of the mRNA stability. Furthermore, we found that several regions around the AREs in the 3'-UTR suppressed the luciferase activity. Moreover, the expression level of the GDNF protein was negligible in C6 glioma cells transfected with the ARE-containing GDNF expression vector.
Our study is the first characterization of the possible role of AREs and other suppressive regions in the 3'-UTR in regulating the amounts of GDNF mRNA in C6 cells.
PMCID: PMC3314560  PMID: 22248285
4.  Role of an ER stress response element in regulating the bidirectional promoter of the mouse CRELD2 - ALG12 gene pair 
BMC Genomics  2010;11:664.
Recently, we identified cysteine-rich with EGF-like domains 2 (CRELD2) as a novel endoplasmic reticulum (ER) stress-inducible gene and characterized its transcriptional regulation by ATF6 under ER stress conditions. Interestingly, the CRELD2 and asparagine-linked glycosylation 12 homolog (ALG12) genes are arranged as a bidirectional (head-to-head) gene pair and are separated by less than 400 bp. In this study, we characterized the transcriptional regulation of the mouse CRELD2 and ALG12 genes that is mediated by a common bidirectional promoter.
This short intergenic region contains an ER stress response element (ERSE) sequence and is well conserved among the human, rat and mouse genomes. Microarray analysis revealed that CRELD2 and ALG12 mRNAs were induced in Neuro2a cells by treatment with thapsigargin (Tg), an ER stress inducer, in a time-dependent manner. Other ER stress inducers, tunicamycin and brefeldin A, also increased the expression of these two mRNAs in Neuro2a cells. We then tested for the possible involvement of the ERSE motif and other regulatory sites of the intergenic region in the transcriptional regulation of the mouse CRELD2 and ALG12 genes by using variants of the bidirectional reporter construct. With regards to the promoter activities of the CRELD2-ALG12 gene pair, the entire intergenic region hardly responded to Tg, whereas the CRELD2 promoter constructs of the proximal region containing the ERSE motif showed a marked responsiveness to Tg. The same ERSE motif of ALG12 gene in the opposite direction was less responsive to Tg. The direction and the distance of this motif from each transcriptional start site, however, has no impact on the responsiveness of either gene to Tg treatment. Additionally, we found three putative sequences in the intergenic region that antagonize the ERSE-mediated transcriptional activation.
These results show that the mouse CRELD2 and ALG12 genes are arranged as a unique bidirectional gene pair and that they may be regulated by the combined interactions between ATF6 and multiple other transcriptional factors. Our studies provide new insights into the complex transcriptional regulation of bidirectional gene pairs under pathophysiological conditions.
PMCID: PMC3091781  PMID: 21106106

Results 1-4 (4)