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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal DOI :
Korean Society for Biochemistry and Molecular Biology
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Volume & Issues
Volume 43, Issue 12 - Dec 2010
Volume 43, Issue 11 - Nov 2010
Volume 43, Issue 10 - Oct 2010
Volume 43, Issue 9 - Sep 2010
Volume 43, Issue 8 - Aug 2010
Volume 43, Issue 7 - Jul 2010
Volume 43, Issue 6 - Jun 2010
Volume 43, Issue 5 - May 2010
Volume 43, Issue 4 - Apr 2010
Volume 43, Issue 3 - Mar 2010
Volume 43, Issue 2 - Feb 2010
Volume 43, Issue 1 - Jan 2010
Selecting the target year
The role of neuroinflammation on the pathogenesis of Parkinson's disease
Chung, Young-Cheul ; Ko, Hyuk-Wan ; Bok, Eu-Gene ; Park, Eun-Soo ; Huh, Sue-Hee ; Nam, Jin-Han ; Jin, Byung-Kwan ;
BMB Reports , volume 43, issue 4, 2010, Pages 225~232
DOI : 10.5483/BMBRep.2010.43.4.225
Parkinson's Disease (PD) is a common neurodegenerative disease characterized by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons. Although the causative factors of PD remain elusive, many studies on PD animal models or humans suggest that glial activation along with neuroinflammatory processes contribute to the initiation or progression of PD. Additionally, several groups have proposed that dysfunction of the blood-brain barrier (BBB) combined with infiltration of peripheral immune cells play important roles in the degeneration of DA neurons. However, these neuroinflammatory events have only been investigated separately, and the issue of whether these phenomena are neuroprotective or neurotoxic remains controversial. We here review the current knowledge regarding the functions of these neuroinflammatory processes in the brain. Finally, we describe therapeutic strategies for the regulation of neuroinflammation with the goal of improving the symptoms of PD.
Biochemical and molecular features of LRRK2 and its pathophysiological roles in Parkinson's disease
Seol, Won-Gi ;
BMB Reports , volume 43, issue 4, 2010, Pages 233~244
DOI : 10.5483/BMBRep.2010.43.4.233
Parkinson's disease (PD) is the second most common neurodegenerative disease, and 5-10% of the PD cases are genetically inherited as familial PD (FPD). LRRK2 (leucine-rich repeat kinase 2) was first reported in 2004 as a gene corresponding to PARK8, an autosomal gene whose dominant mutations cause familial PD. LRRK2 contains both active kinase and GTPase domains as well as protein-protein interaction motifs such as LRR (leucine-rich repeat) and WD40. Most pathogenic LRRK2 mutations are located in either the GTPase or kinase domain, implying important roles for the enzymatic activities in PD pathogenic mechanisms. In comparison to other PD causative genes such as parkin and PINK1, LRRK2 exhibits two important features. One is that LRRK2's mutations (especially the G2019S mutation) were observed in sporadic as well as familial PD patients. Another is that, among the various PD-causing genes, pathological characteristics observed in patients carrying LRRK2 mutations are the most similar to patients with sporadic PD. Because of these two observations, LRRK2 has been intensively investigated for its pathogenic mechanism (s) and as a target gene for PD therapeutics. In this review, the general biochemical and molecular features of LRRK2, the recent results of LRRK2 studies and LRRK2's therapeutic potential as a PD target gene will be discussed.
Inhibitory effects of KHG26377 on glutamate dehydrogenase activity in cultured islets
Yang, Seung-Ju ; Hahn, Hoh-Gyu ; Choi, Soo-Young ; Cho, Sung-Woo ;
BMB Reports , volume 43, issue 4, 2010, Pages 245~249
DOI : 10.5483/BMBRep.2010.43.4.245
GDH has been known to be related with hyperinsulinism-hyperammonemia syndrome. We have screened new drugs with a view to developing effective drugs modulating GDH activity. In the present work, we investigated the effects of a new drug, KHG26377 on glutamate formation and GDH activity in cultured rat islets. When KHG26377 was added to the culture medium for 24 h prior to kinetic analysis, the
of GDH was decreased by 59% whereas
is not significantly changed. The concentration of glutamate decreased by 50% and perfusion of islets with KHG26377 reduced insulin release by up to 55%. Our results show that KHG26377 regulates insulin release by inhibiting GDH activity in primary cultured islets and support the previous studies for the connection between GDH activity and insulin release. Further studies are required to determine in vivo effects and pharmacokinetics of the drug.
Enhancement of immunomodulatory activity by liposome-encapsulated natural phosphodiester bond CpG-DNA in a human B cell line
Kim, Dong-Bum ; Rhee, Jae-Won ; Kwon, Sang-Hoon ; Kim, Young-Eun ; Choi, Soo-Young ; Park, Jin-Seu ; Lee, Young-Hee ; Kwon, Hyung-Joo ;
BMB Reports , volume 43, issue 4, 2010, Pages 250~256
DOI : 10.5483/BMBRep.2010.43.4.250
Natural phosphodiester bond CpG-DNA that contains immunomodulatory CpG motifs (PO-DNA) upregulates the expression of proinflammatory cytokines and induces an Ag-driven Th1 response in a CG sequence-dependent manner in mice. In humans, only phosphorothioate backbone-modified CpG-DNA (PS-DNA) and not PO-DNA has immunomodulatory activity. In this study, we found that liposome-encapsulated PO-DNA upregulated the expression of human
-defensin-2 (hBD-2) and major histocompatibility class II molecules (HLA-DRA) in a CG sequence-dependent and liposome- dependent manner in human B cells. Of the three different liposomes, DOTAP has the unique ability to enhance the immunomodulatory activity of PO-DNA. In contrast, HLA-DRA and hBD-2 promoter activation can be induced by liposome-encapsulated PS-DNA in a CG sequence-independent manner, depending on the CpG-DNA species. Our observations demonstrate that, when encapsulated with a proper liposome in the immune system, natural PO-DNA has the potential to be a useful therapy for the regulation of the innate immune response.
Influence of the lung mechanical ventilation with injurious parameters on 7-ketocholesterol synthesis in Sus Scrofa
Klimenko, Oxana V. ; Vobruba, Vaclav ; Martasek, Pavel ;
BMB Reports , volume 43, issue 4, 2010, Pages 257~262
DOI : 10.5483/BMBRep.2010.43.4.257
The aim of work was to investigate changes of 7-ketocholesterol synthesis in alveolar macrophages in the dynamic of lung mechanical ventilation with injurious parameters. The goal of in vitro part of work was to observe influence of 7-ketocholesterol on iNOS and MIP1
production in bronchoalveolar lavage fluid (BALF) cells. We used 17 healthy domestic pigs randomly assigned into two treatment groups: group I with mechanical ventilation with physiological parameters; group II underwent injurious ventilation with high volume tidal (VT) and low positive end expiratory pressure (PEEP). Cells were analyzed for CYP27A1 protein and gene expression levels, 7-ketocholesterol production. In alveolar macrophages of group II, we obtained increase of production of CYP27A1 protein and 7-ketocholesterol, as well as the expression of the CYP27A1 gene at the 2nd hour of ventilation. In the in vitro experiments we show dose-dependent increase of MIP1
and decrease of CYP27A1, iNOS protein production after 7-ketocholesterol treatment.
Phosphorylation on the PPP2R5D B regulatory subunit modulates the biochemical properties of protein phosphatase 2A
Yu, Un-Young ; Ahn, Jung-Hyuck ;
BMB Reports , volume 43, issue 4, 2010, Pages 263~267
DOI : 10.5483/BMBRep.2010.43.4.263
To characterize the biochemical properties of the PP2A regulatory B subunit, PPP2R5D, we analyzed its phosphorylation sites, stoichiometry and effect on holoenzyme activity. PPP2R5D was phosphorylated on Ser-53, Ser-68, Ser-81, and Ser-566 by protein kinase A, and mutations at all four of these sites abolished any significant phosphorylation in vitro. In HEK293 cells, however, the Ser-566 was the major phosphorylation site after PKA activation by forskolin, with marginal phosphorylation on Ser-81. Inhibitory tyrosine phosphorylation on Tyr-307 of the PP2A catalytic C subunit was decreased after forskolin treatment. Kinetic analysis showed that overall PP2A activity was increased with phosphorylation by PPP2R5D phosphorylation. The apparent Km was reduced from
with PPP2R5D phosphorylation, resulting in an increase in catalytic activity. These data suggest that PKA-mediated activation of PP2A is enabled by PPP2R5D phosphorylation, which modulates the affinity of the PP2A holoenzyme to its physiological substrates.
Inhibitory effects of polyphenols isolated from Rhus verniciflua on Aldo-keto reductase family 1 B10
Song, Dae-Geun ; Lee, Joo-Young ; Lee, Eun-Ha ; Jung, Sang-Hoon ; Nho, Chu-Won ; Cha, Kwang-Hyun ; Koo, Song-Yi ; Pan, Cheol-Ho ;
BMB Reports , volume 43, issue 4, 2010, Pages 268~272
DOI : 10.5483/BMBRep.2010.43.4.268
Aldo-keto reductase family 1 B10 (AKR1B10) is a member of the NADPH-dependent aldo-keto reductase (AKR) superfamily, and has been considered to be a potential cancer therapeutic target. Total extract from the bark of Rhus verniciflua (Toxicodendron vernicifluum (Stokes)) showed AKR1B10 inhibitory activity. To identify the active compounds from R. verniciflua responsible for AKR1B10 inhibition, nine compounds were isolated via bioactivity-guided isolation and tested for their effects against recombinant human AKR1B10 (rhAKR1B10). Results showed that butein, isolated from the ethyl acetate fraction, was most able to inhibit rhAKR1B10. The inhibitory rate of butein against rhAKR1B10 was 42.86% at
with an IC50 value of
, and enzyme kinetic analysis revealed its inhibition mode to be uncompetitive.
Expression of Kip-related protein 4 gene (KRP4) in response to auxin and cytokinin during growth of Arabidopsis thalia
Cho, Hye-Jeong ; Kwon, Hye-Kyoung ; Wang, Myeong-Hyeon ;
BMB Reports , volume 43, issue 4, 2010, Pages 273~278
DOI : 10.5483/BMBRep.2010.43.4.273
The cell cycle is regulated by cyclin-dependent kinase (CDK)-cyclin complexes as well as other regulators. We isolated Kip-related protein 4 (KRP4) cDNA that encodes 289 amino acids including six conserved domains. To investigate the expression pattern of KRP4 as well as of other cell cycle-related genes associated with plant hormones, Arabidopsis seedlings were cultured on MS medium containing auxin or cytokinin. All seedlings treated with phytohormones displayed an increased proportion of cells in S phase. A higher proportion of cells in G2 phase was observed in seedlings treated with NAA. RT-PCR confirmed that the expression of KRP4 was decreased after treatment with phytohormones, and that CDKA and D-type cyclin transcription was increased. Additionally, mitotic cyclins were up-regulated by NAA treatment. These results suggest that KRP4 as well as other cell cycle-related genes might contribute to the control of plant growth in response to exogenous hormones.
A SERI technique reveals an immunosuppressive activity of a serine-rich protein encoded in Cotesia plutellae bracovirus
Barandoc, Karen P. ; Park, Jay-Young ; Kim, Yong-Gyun ;
BMB Reports , volume 43, issue 4, 2010, Pages 279~283
DOI : 10.5483/BMBRep.2010.43.4.279
Polydnavirus genome is segmented and dispersed on host wasp chromosome. After replication, the segments form double- stranded circular DNAs and embedded in viral coat proteins. These viral particles are delivered into a parasitized host along with parasitoid eggs. A serine-rich protein (SRP) is predicted in a polydnavirus, Cotesia plutellae bracovirus (CpBV), genome in its segment no. 33 (CpBV-S33), creating CpBV-SRP1. This study explored its expression and physiological function in the diamondback moth, Plutella xylostella, larvae parasitized by C. plutellae. CpBV-SRP1 encodes 122 amino acids with 26 serines and several predicted phosphorylation sites. It is persistently expressed in all tested tissues of parasitized P. xylostella including hemocyte, fat body, and gut. Its physiological function was analyzed by injecting CpBV-S33 and inducing its expression in nonparasitized P. xylostella by a technique called SERI (segment expression and RNA interference). The expression of CpBV-SRP1 significantly impaired the spreading behavior and total cell count of hemocytes of treated larvae. Subsequent RNA interference of CpBV-SRP1 rescued the immunosuppressive response. This study reports the persistent expression of CpBV-SRP1 in a parasitized host and its parasitic role in suppressing the host immune response by altering hemocyte behavior and survival.
Expression and characterization of RNA-dependent RNA polymerase of Ectropis obliqua virus
Lin, Meijuan ; Ye, Shan ; Xiong, Yi ; Cai, Dawei ; Zhang, Jiamin ; Hu, Yuanyang ;
BMB Reports , volume 43, issue 4, 2010, Pages 284~290
DOI : 10.5483/BMBRep.2010.43.4.284
Replication of positive-strand RNA virus is mediated by a virus-encoded RNA-dependent RNA polymerase (RdRp). To study the replication of Ectropis obliqua virus (EoV), a newly identified insect virus belonging to the family Iflaviradae, we expressed the RNA polymerase domain in Escherichia coli and purified it on a Ni-chelating HisTrap affinity column. It is demonstrated that EoV RdRp initiated RNA synthesis in a primer and poly (A)-dependent manner in vitro. Furthermore, the effect of primer concentration, temperature, metal ions (
) on enzymatic activity were determined. Our study represented a first step towards understanding the mechanism of EoV replication.
Suppression of CDK2 expression by siRNA induces cell cycle arrest and cell proliferation inhibition in human cancer cells
Long, Xiang-E. ; Gong, Zhao-Hui ; Pan, Lin ; Zhong, Zhi-Wei ; Le, Yan-Ping ; Liu, Qiong ; Guo, Jun-Ming ; Zhong, Jiu-Chang ;
BMB Reports , volume 43, issue 4, 2010, Pages 291~296
DOI : 10.5483/BMBRep.2010.43.4.291
Cyclin-dependent kinase 2 (CDK2) is a member of serine/threonine protein kinases, which initiates the principal transitions of the eukaryotic cell cycle and is a promising target for cancer therapy. The present study was designed to inhibit cdk2 gene expression to induce cell cycle arrest and cell proliferation suppression. Here, we constructed a series of RNA interference (RNAi) plasmids which can successfully express small interference RNA (siRNA) in the transfected human cells. The results showed that the RNAi plasmids containing the coding sequences for siRNAs down-regulated the cdk2 gene expression in human cancer cells at the mRNA and the protein levels. Furthermore, we found that the cell cycle was arrested at G0G1 phases and the cell proliferation was inhibited by different siRNAs. These results demonstrate that suppression of CDK2 activity by RNAi may be an effective strategy for gene therapy in human cancers.
Baicalein and wogonin inhibit collagen deposition in SHR and WKY cardiac fibroblast cultures
Kong, Ebenezer K.C. ; Huang, Yu ; Sanderson, John E. ; Chan, Kar-Bik ; Yu, Shan ; Yu, Cheuk-Man ;
BMB Reports , volume 43, issue 4, 2010, Pages 297~303
DOI : 10.5483/BMBRep.2010.43.4.297
In order to demonstrate the potential therapeutic effect of two flavonoids, Baicalein and Wogonin, on suppression of pathological myocardial fibrosis in hypertension, we investigated their in vitro effects on collagen expression in primary cultured cardiac fibroblasts isolated from neonatal normotensive (WKY) and hypertensive (SHR) rats. Our results showed that over-expression of collagen mRNA and protein induced in cardiac fibroblasts by angiotensin (AngII) could be attenuated significantly by both flavonoids at an optimal dosage (
; P < 0.01). Results of immunoblots showed that expression of 12-LO level, p-ERK/ ERK ratio and MMP-9 in AngII-stimulated SHR cardiac fibroblasts were significantly down-regulated by both flavonoids. Our results show that both Baicalein and Wogonin can suppress collagen deposition in AngII-stimulated SHR and WKY cardiac fibroblasts.