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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Korean Society for Biochemistry and Molecular Biology
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Volume & Issues
Volume 49, Issue 9 - Sep 2016
Volume 49, Issue 8 - Aug 2016
Volume 49, Issue 7 - Jul 2016
Volume 49, Issue 6 - Jun 2016
Volume 49, Issue 5 - May 2016
Volume 49, Issue 4 - Apr 2016
Volume 49, Issue 3 - Mar 2016
Volume 49, Issue 2 - Feb 2016
Volume 49, Issue 1 - Jan 2016
Selecting the target year
Donating Otx2 to support neighboring neuron survival
Kim, Hyoung-Tai ; Prochiantz, Alain ; Kim, Jin Woo ;
BMB Reports , volume 49, issue 2, 2016, Pages 69~70
DOI : 10.5483/BMBRep.2016.49.2.006
Mutations of orthodentricle homeobox 2 (OTX2) in human and mice often cause retinal dystrophy and nyctalopia, suggesting a role of OTX2 in mature retina, in addition to its functions in the development of the eye and retina. In support of this, the number of bipolar cells in Otx2
post-natal mouse retina was found to be significantly lower than normal. Degeneration of the cells becomes greater as the mice age, leading to the loss of vision. Especially, the type-2 OFF-cone bipolar cells, which do not express Otx2 mRNA but carry Otx2 protein, are most sensitive to Otx2 haplodeficiency. Interestingly, this bipolar cell subpopulation imports Otx2 protein from photoreceptors to protect itself from glutamate excitotoxicity in the dark. Moreover, in the bipolar cells, the exogenous Otx2 relocates to the mitochondria to support mitochondrial ATP synthesis. This novel mitochondrial activity of exogenous Otx2 highlights the therapeutic potential of Otx2 protein transduction in retinal dystrophy.
Brain somatic mutations in MTOR leading to focal cortical dysplasia
Lim, Jae Seok ; Lee, Jeong Ho ;
BMB Reports , volume 49, issue 2, 2016, Pages 71~72
DOI : 10.5483/BMBRep.2016.49.2.010
Focal cortical dysplasia type II (FCDII) is a focal malformation of the developing cerebral cortex and the major cause of intractable epilepsy. However, since the molecular genetic etiology of FCD has remained enigmatic, the effective therapeutic target for this condition has remained poorly understood. Our recent study on FCD utilizing various deep sequencing platforms identified somatic mutations in MTOR (existing as low as 1% allelic frequency) only in the affected brain tissues. We observed that these mutations induced hyperactivation of the mTOR kinase. In addition, focal cortical expression of mutant MTOR using in utero electroporation in mice, recapitulated the neuropathological features of FCDII, such as migration defect, cytomegalic neuron and spontaneous seizures. Furthermore, seizures and dysmorphic neurons were rescued by the administration of mTOR inhibitor, rapamycin. This study provides the first evidence that brain somatic activating mutations in MTOR cause FCD, and suggests the potential drug target for intractable epilepsy in FCD patients.
Structure biology of selective autophagy receptors
Kim, Byeong-Won ; Kwon, Do Hoon ; Song, Hyun Kyu ;
BMB Reports , volume 49, issue 2, 2016, Pages 73~80
DOI : 10.5483/BMBRep.2016.49.2.265
Autophagy is a process tightly regulated by various autophagy-related proteins. It is generally classified into non-selective and selective autophagy. Whereas non-selective autophagy is triggered when the cell is under starvation, selective autophagy is involved in eliminating dysfunctional organelles, misfolded and/or ubiquitylated proteins, and intracellular pathogens. These components are recognized by autophagy receptors and delivered to phagophores. Several selective autophagy receptors have been identified and characterized. They usually have some common domains, such as motif, a specific cargo interacting (ubiquitin-dependent or ubiquitin-independent) domain. Recently, structural data of these autophagy receptors has been described, which provides an insight of their function in the selective autophagic process. In this review, we summarize the most up-to-date findings about the structure-function of autophagy receptors that regulates selective autophagy.
The role of insulin/IGF-1 signaling in the longevity of model invertebrates, C. elegans and D. melanogaster
Altintas, Ozlem ; Park, Sangsoon ; Lee, Seung-Jae V. ;
BMB Reports , volume 49, issue 2, 2016, Pages 81~92
DOI : 10.5483/BMBRep.2016.49.2.261
Insulin/insulin-like growth factor (IGF)-1 signaling (IIS) pathway regulates aging in many organisms, ranging from simple invertebrates to mammals, including humans. Many seminal discoveries regarding the roles of IIS in aging and longevity have been made by using the roundworm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. In this review, we describe the mechanisms by which various IIS components regulate aging in C. elegans and D. melanogaster. We also cover systemic and tissue-specific effects of the IIS components on the regulation of lifespan. We further discuss IIS-mediated physiological processes other than aging and their effects on human disease models focusing on C. elegans studies. As both C. elegans and D. melanogaster have been essential for key findings regarding the effects of IIS on organismal aging in general, these invertebrate models will continue to serve as workhorses to help our understanding of mammalian aging.
A systematic mRNA control mechanism for germline stem cell homeostasis and cell fate specification
Lee, Myon-Hee ; Mamillapalli, Srivalli Swathi ; Keiper, Brett D. ; Cha, Dong Seok ;
BMB Reports , volume 49, issue 2, 2016, Pages 93~98
DOI : 10.5483/BMBRep.2016.49.2.135
Germline stem cells (GSCs) are the best understood adult stem cell types in the nematode Caenorhabditis elegans, and have provided an important model system for studying stem cells and their cell fate in vivo, in mammals. In this review, we propose a mechanism that controls GSCs and their cell fate through selective activation, repression and mobilization of the specific mRNAs. This mechanism is acutely controlled by known signal transduction pathways (e.g., Notch signaling and Ras-ERK MAPK signaling pathways) and P granule (analogous to mammalian germ granule)-associated mRNA regulators (FBF-1, FBF-2, GLD-1, GLD-2, GLD-3, RNP-8 and IFE-1). Importantly, all regulators are highly conserved in many multi-cellular animals. Therefore, GSCs from a simple animal may provide broad insight into vertebrate stem cells (e.g., hematopoietic stem cells) and their cell fate specification.
Non-histone protein HMGB1 inhibits the repair of damaged DNA by cisplatin in NIH-3T3 murine fibroblasts
Yusein-Myashkova, Shazie ; Ugrinova, Iva ; Pasheva, Evdokia ;
BMB Reports , volume 49, issue 2, 2016, Pages 99~104
DOI : 10.5483/BMBRep.2016.49.2.238
The nuclear non-histone protein high mobility group box (HMGB) 1 is known to having an inhibitory effect on the repair of DNA damaged by the antitumor drug cisplatin in vitro. To investigate the role of HMGB1 in living cells, we studied the DNA repair of cisplatin damages in mouse fibroblast cell line, NIH-3T3. We evaluated the effect of the post-synthetic acetylation and C-terminal domain of the protein by overexpression of the parental and mutant GFP fused forms of HMGB1. The results revealed that HMGB1 had also an inhibitory effect on the repair of cisplatin damaged DNA in vivo. The silencing of HMGB1 in NIH-3T3 cells increased the cellular DNA repair potential. The increased levels of repair synthesis could be "rescued" and returned to less than normal levels if the knockdown cells were transfected with plasmids encoding HMGB1 and HMGB1 K2A. In this case, the truncated form of HMGB1 also exhibited a slight inhibitory effect.
Ursodeoxycholic acid decreases age-related adiposity and inflammation in mice
Oh, Ah-Reum ; Bae, Jin-Sik ; Lee, Junghoon ; Shin, Eunji ; Oh, Byung-Chul ; Park, Sang-Chul ; Cha, Ji-Young ;
BMB Reports , volume 49, issue 2, 2016, Pages 105~110
DOI : 10.5483/BMBRep.2016.49.2.173
Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli.
Caffeine inhibits adipogenesis through modulation of mitotic clonal expansion and the AKT/GSK3 pathway in 3T3-L1 adipocytes
Kim, Hyo Jung ; Yoon, Bo Kyung ; Park, Hyounkyoung ; Seok, Jo Woon ; Choi, Hyeonjin ; Yu, Jung Hwan ; Choi, Yoonjeong ; Song, Su Jin ; Kim, Ara ; Kim, Jae-woo ;
BMB Reports , volume 49, issue 2, 2016, Pages 111~115
DOI : 10.5483/BMBRep.2016.49.2.128
Caffeine has been proposed to have several beneficial effects on obesity and its related metabolic diseases; however, how caffeine affects adipocyte differentiation has not been elucidated. In this study, we demonstrated that caffeine suppressed 3T3-L1 adipocyte differentiation and inhibited the expression of CCAAT/enhancer binding protein (C/EBP)α and peroxisome proliferator-activated receptor (PPAR)γ, two main adipogenic transcription factors. Anti-adipogenic markers, such as preadipocyte secreted factor (Pref)-1 and Krüppel-like factor 2, remained to be expressed in the presence of caffeine. Furthermore, 3T3-L1 cells failed to undergo typical mitotic clonal expansion in the presence of caffeine. Investigation of hormonal signaling revealed that caffeine inhibited the activation of AKT and glycogen synthase kinase (GSK) 3 in a dose-dependent manner, but not extracellular signal-regulated kinase (ERK). Our data show that caffeine is an anti-adipogenic bioactive compound involved in the modulation of mitotic clonal expansion during adipocyte differentiation through the AKT/GSK3 pathway.
Mitochondrial oxidative phosphorylation complexes exist in the sarcolemma of skeletal muscle
Lee, Hyun ; Kim, Seung-Hyeob ; Lee, Jae-Seon ; Yang, Yun-Hee ; Nam, Jwa-Min ; Kim, Bong-Woo ; Ko, Young-Gyu ;
BMB Reports , volume 49, issue 2, 2016, Pages 116~121
DOI : 10.5483/BMBRep.2016.49.2.232
Although proteomic analyses have revealed the presence of mitochondrial oxidative phosphorylation (OXPHOS) proteins in the plasma membrane, there have been no in-depth evaluations of the presence or function of OXPHOS I-V in the plasma membrane. Here, we demonstrate the in situ localization of OXPHOS I-V complexes to the sarcolemma of skeletal muscle by immunofluorescence and immunohistochemistry. A portion of the OXPHOS I-V complex proteins was not co-stained with MitoTracker but co-localized with caveolin-3 in the sarcolemma of mouse gastrocnemius. Mitochondrial matrix-facing OXPHOS complex subunits were ectopically expressed in the sarcolemma of the non-permeabilized muscle fibers and C2C12 myotubes. The sarcolemmal localization of cytochrome c was also observed from mouse gastrocnemius muscles and C2C12 myotubes, as determined by confocal and total internal resonance fluorescence (TIRF) microscopy. Based on these data, we conclude that a portion of OXPHOS complexes is localized in the sarcolemma of skeletal muscle and may have non-canonical functions.
IGF1 potentiates BMP9-induced osteogenic differentiation in mesenchymal stem cells through the enhancement of BMP/Smad signaling
Chen, Liang ; Zou, Xiang ; Zhang, Ran-Xi ; Pi, Chang-Jun ; Wu, Nian ; Yin, Liang-Jun ; Deng, Zhong-Liang ;
BMB Reports , volume 49, issue 2, 2016, Pages 122~127
DOI : 10.5483/BMBRep.2016.49.2.228
Engineered bone tissue is thought to be the ideal alternative for bone grafts in the treatment of related bone diseases. BMP9 has been demonstrated as one of the most osteogenic factors, and enhancement of BMP9-induced osteogenesis will greatly accelerate the development of bone tissue engineering. Here, we investigated the effect of insulin-like growth factor 1 (IGF1) on BMP9-induced osteogenic differentiation, and unveiled a possible molecular mechanism underling this process. We found that IGF1 and BMP9 are both detectable in mesenchymal stem cells (MSCs). Exogenous expression of IGF1 potentiates BMP9-induced alkaline phosphatase (ALP), matrix mineralization, and ectopic bone formation. Similarly, IGF1 enhances BMP9-induced endochondral ossification. Mechanistically, we found that IGF1 increases BMP9-induced activation of BMP/Smad signaling in MSCs. Our findings demonstrate that IGF1 can enhance BMP9-induced osteogenic differentiation in MSCs, and that this effect may be mediated by the enhancement of the BMP/Smad signaling transduction triggered by BMP9.
Epac2 contributes to PACAP-induced astrocytic differentiation through calcium ion influx in neural precursor cells
Seo, Hyunhyo ; Lee, Kyungmin ;
BMB Reports , volume 49, issue 2, 2016, Pages 128~133
DOI : 10.5483/BMBRep.2016.49.2.202
Astrocytes play a critical role in normal brain functions and maintaining the brain microenvironment, and defects in astrocytogenesis during neurodevelopment could give rise to severe mental illness and psychiatric disorders. During neuro-embryogenesis, astrocytogenesis involves astrocytic differentiation of neural precursor cells (NPCs) induced by signals from ciliary neurotrophic factor (CNTF) or pituitary adenylate cyclase-activating peptide (PACAP). However, in contrast to the CNTF signaling pathway, the exact mechanism underlying astrocytic differentiation induced by PACAP is unknown. In the present study, we aimed to verify a signaling pathway specific to PACAP-induced astrocytogenesis, using exchange protein directly activated by cAMP2 (Epac2)-knockout mice. We found that PACAP could trigger astrocytic differentiation of NPCs via Epac2 activation and an increase in the intracellular calcium concentration via a calcium ion influx. Taken together, we concluded that astrocytogenesis stimulated by PACAP occurs through a novel signaling pathway independent from CNTF-JAK/STAT signaling, that is the well-known pathway of astrocytogenesis.