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BMB Reports

Jeongjin Kim, Daesoo Kim
Parkinson's disease (PD) is a debilitating disorder resulting from loss of dopamine neurons. In dopamine deficient state, the basal ganglia increases inhibitory synaptic outputs to the thalamus. This increased inhibition by the basal ganglia output is known to reduce firing rate of thalamic neurons that relay motor signals to the motor cortex. This 'rate model' suggests that the reduced excitability of thalamic neurons is the key for inducing motor abnormalities in PD patients. We reveal that in response to inhibition, thalamic neurons generate rebound firing at the end of inhibition...
January 16, 2018: BMB Reports
Songhwa Kang, Jisoo Yun, Da Yeon Kim, Seok Yun Jung, Yeon Ju Kim, Ji Hye Park, Seung Taek Ji, Woong Bi Jang, Joungsung Ha, Jae Ho Kim, Sang Hong Baek, Sang-Mo Kwon
B cell leukemia/lymphoma 3 (Bcl3) plays a pivotal role in immune homeostasis, cellular proliferation, and cell survival, as a co-activator or co-repressor of transcription of the NF-κB family. Recently, it was reported that Bcl3 positively regulates pluripotency genes, including Oct4, in mouse embryonic stem cells (mESCs). However, the role of Bcl3 in the maintenance of pluripotency and self-renewal activity is not fully established. Here, we report the dynamic regulation of the proliferation, pluripotency, and self-renewal of mESCs by Bcl3 via an influence on Nanog transcriptional activity...
January 16, 2018: BMB Reports
Hye-Eun Kim, Hyejoung Cho, Atsushi Ishihara, Byungkuk Kim, Okjoon Kim
Caffeoylserotonin (CaS), one derivative of serotonin (5-HT), is a secondary metabolite produced in pepper fruits with strong antioxidant activities. In this study, we investigated the effect of CaS on proliferation and migration of human keratinocyte HaCaT cells compared to that of 5-HT. CaS enhanced keratinocyte proliferation even under serum deficient condition. This effect of CaS was mediated by serotonin 2B receptor (5-HT2BR) related to the cell proliferation effect of 5-HT. We also confirmed that both CaS and 5-HT induced G1 progression via 5-HT2BR/ERK pathway in HaCaT cells...
January 16, 2018: BMB Reports
Jonghyun Choi, Yongwoo Jang, Haedong Kim, Jungwon Wee, Sinyoung Cho, Woo Sung Son, Sung Min Kim, Young Duk Yang
Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic Ca2+ concentration and noxious heat. Although the critical roles of ANO1 have been elucidated in various cell types, the control of its gating mechanisms by Ca2+ and heat remain more elusive. To investigate critical amino acid residues for modulation of Ca2+ and heat sensing, we constructed a randomized mutant library for ANO1. Among 695 random mutants, reduced Ca2+ sensitivity was observed in two mutants (mutant 84 and 87). Consequently, the E143A mutant showed reduced sensitivity to Ca2+ but not to high temperatures, whereas the E705V mutant exhibited reduced sensitivity to both Ca2+ and noxious heat...
January 16, 2018: BMB Reports
Yoo-Wook Kwon, Hyo-Suk Ahn, Joo-Young Park, Han-Mo Yang, Hyun-Jai Cho, Hyo-Soo Kim
Induced pluripotent stem cells (iPSCs) show great promise for replacing current stem cell therapies in the field of regenerative medicine. However, the original method for cellular reprogramming, involving four exogenous transcription factors, is characterized by low efficiency. Here, we focused on using epigenetic modifications to enhance the reprogramming efficiency. We hypothesized that there would be a new reprogramming factor involved in DNA demethylation, acting on the promoters of pluripotency-related genes...
January 16, 2018: BMB Reports
Chang-Hwan Yoon, Tae-Won Kim, Seok-Jin Koh, Young-Eun Choi, Jin Hur, Yoo-Wook Kwon, Hyun-Jai Cho, Hyo-Soo Kim
Pluripotent stem cell (PSC) variations can cause significant differences in the efficiency of cardiac differentiation. This process is unpredictable, as there is not an adequate indicator at the undifferentiated stage of the PSCs. We compared global gene expression profiles of two PSCs showing significant differences in cardiac differentiation potential. We identified 12 up-regulated genes related to heart development, and we found that 4 genes interacted with multiple genes. Among these genes, Gata6 is the only gene that was significantly induced at the early stage of differentiation of PSCs to cardiomyocytes...
January 16, 2018: BMB Reports
Tae Hwan Shin, Da Yeon Lee, Hyeon-Seong Lee, Hyung Jin Park, Moon Suk Jin, Man-Jeong Paik, Balachandran Manavalan, Jung-Soon Mo, Gwang Lee
Biomedical research involving nanoparticles has produced useful products with medical applications. However, the potential toxicity of nanoparticles in biofluids, cells, tissues, and organisms is a major challenge. The '-omics' analyses provide molecular profiles of multifactorial biological systems instead of focusing on a single molecule. The 'omics' approaches are necessary to evaluate nanotoxicity because classical methods for the detection of nanotoxicity have limited ability in detecting miniscule variations within a cell and do not accurately reflect the actual levels of nanotoxicity...
January 5, 2018: BMB Reports
Jin-Man Kim, Kyunghee Lee, Daewon Jeong
Bone resorption by multinucleated osteoclasts is a multistep process involving adhesion to the bone matrix, migration to resorption sites, and formation of sealing zones and ruffled borders. Macrophage colony-stimulating factor (M-CSF) and osteopontin (OPN) have been shown to be involved in the bone resorption process by respective activation of integrin αvβ3 via "inside-out" and "outside-in" signaling. In this study, we investigated the link between signal modulators known to M-CSF- and OPN-induced osteoclast adhesion and spreading...
January 5, 2018: BMB Reports
Eun-Jung Lim, Yongjoon Suh, Seungmo Kim, Seok-Gu Kang, Su-Jae Lee
In carcinoma, cancer-associated fibroblasts participate in force-mediated extracellular matrix (ECM) remodeling, consequently leading to invasion of cancer cells. Likewise, the ECM remodeling actively occurs in glioblastoma (GBM) and the consequent microenvironmental stiffness is strongly linked to migration behavior of GBM cells. However, in GBM the stromal cells responsible for force-mediated ECM remodeling remain unidentified. We show that tumor-associated mesenchymal stem-like cells (tMSLCs) provide a proinvasive matrix condition in GBM by force-mediated ECM remodeling...
January 5, 2018: BMB Reports
Seung-Eun Song, Su-Kyung Shin, So-Young Park, Il-Seon Hwang, Seung-Soon Im, Jae-Hoon Bae, Myung-Sook Choi, Dae-Kyu Song
Exchange protein directly activated by cAMP (Epac) 2a-knockout (KO) mice exhibit accelerated diet-induced obesity and are resistant to leptin-mediated adipostatic signaling from the hypothalamus to adipose tissue, with sustained food intake. However, the impact of Epac2a deficiency on hypothalamic regulation of sympathetic nervous activity (SNA) has not been elucidated. This study was performed to elucidate the response of Epac2a-KO mice to dexamethasone-induced muscle atrophy and acute cold stress. Compared to age-matched wild-type mice, Epac2a-KO mice showed higher energy expenditures and expression of myogenin and uncoupling protein-1 in skeletal muscle (SM) and brown adipose tissue (BAT), respectively...
January 5, 2018: BMB Reports
Min Bum Lee, JunHo Lee, Seong Hwi Hong, Jueng Soo You, Seung Taek Nam, Hyun Woo Kim, Young Hwan Park, Dajeong Lee, Keun Young Min, Yeong-Min Park, Young Mi Kim, Hyuk Soon Kim, Wahn Soo Choi
Regulatory B cells, also well-known as IL-10-producing B cells, play a role in the suppression of inflammatory responses. However, the epigenetic modulation of regulatory B cells is largely unknown. Recent studies showed that the bromodomain and extra-terminal domain (BET) protein inhibitor JQ1 controls the expression of various genes involving cell proliferation and cell cycle. However, the role of BET proteins on development of regulatory B cells is not reported. In this study, JQ1 potently suppressed IL-10 expression and secretion in murine splenic and peritoneal B cells...
November 29, 2017: BMB Reports
Boram Min, Kwang Chul Chung
Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional enzyme, displaying four types of activity, such as transamidation, GTPase, protein disulfide isomerase, and protein kinase activities. Many studies demonstrated that the calcium-dependent transamidation activity of TG2 affected the formation of insoluble and toxic amyloid aggregates that mainly consisted of NDD-related proteins...
November 29, 2017: BMB Reports
Yuseob Kim
Positive selection on a new beneficial mutation generates a characteristic pattern of DNA sequence polymorphism when it reaches an intermediate allele frequency. On genome sequences of African Drosophila melanogaster, we detected such signatures of selection at 37 candidate loci and identified "sweeping haplotypes (SHs)" that are increasing or have increased rapidly in frequency due to hitchhiking. Based on geographic distribution of SH frequencies, we could infer whether selective sweeps occurred starting from de novo beneficial mutants under simple constant selective pressure...
November 29, 2017: BMB Reports
Byung In Choe, Gwi Hyang Lee
Scientists planning research that involves the use of animals are required to examine the possibilities for replacement, reduction, or refinement (the Three Rs), and their protocol must be reviewed by the Institutional Animal Care and Use Committee. Good scientific practice involving appropriate search techniques on the available Three Rs resources is essential for both ethical and scientific reasons. Appropriate experimental design and statistical analysis techniques are particularly necessary for research involving the use of animals, because this can improve animal welfare and scientific outcomes, as well as saving animal lives...
November 29, 2017: BMB Reports
Xueliang Yang, Ming Han, Shunai Liu, Xiaoxue Yuan, Xiaojing Liu, Shenghu Feng, Li Zhou, Yaru Li, Hongping Lu, Jun Cheng, Shumei Lin
Sterol regulatory element-binding protein-1c (SREBP1c) plays an important role in triglyceride (TG) homeostasis. Although our previous study showed that hepatitis C virus core-binding protein 6 (HCBP6) regulates SREBP1c expression to maintain intracellular TG homeostasis, the mechanism underlying this regulation is unclear. In the present study, we found that HCBP6 increased intracellular TG levels by upregulating SREBP1c expression. HCBP6 increased SREBP1c transcription by directly binding to the SREBP1c promoter (at the -139- to +359-bp region)...
November 20, 2017: BMB Reports
Muhammad Ali, Shazia Anwer Bukhari, Muhammad Ali, Han-Woong Lee
Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained...
October 30, 2017: BMB Reports
Ji Hye Han, Ae Ran Moon, Jeong Hwan Chang, Jeehyeon Bae, Jin Myung Choi, Sung Haeng Lee, Tae-Hyoung Kim
The BMB Reports would like to correct in the ACKNOWLEDGEMENTS of BMB Rep. 49(5), 282-287 titled "Potentiation of TRAIL killing activity by multimerization through isoleucine zipper hexamerization motif."
December 2017: BMB Reports
Hyuk Moon, Kwang-Hyub Han, Simon Weonsang Ro
Many studies have focused on the tumor suppressive role of TGF-β signaling during the early stages of tumorigenesis by activating the target genes involved in cytostasis and apoptosis. We investigated the effects of TGF-β inhibition on early tumorigenesis in the liver, by employing diverse inhibitory methods. Strikingly, TGF-β inhibition consistently suppressed hepatic tumorigenesis that was induced either by activated RAS plus p53 downregulation or by the co-activation of RAS and TAZ signaling; this demonstrates the requirements for canonical TGF-β signaling in tumorigenesis...
October 25, 2017: BMB Reports
Hyunsung Park
Hypoxia affects various physiological and pathophyological processes. Hypoxia changes the expression of the hypoxia-responsive genes through two main pathways. First, hypoxia activates transcription factors (TF) such as Hypoxia-inducible Factor (HIF). Second, hypoxia decreases the activity of Jumonji C domain-containing histone demethylases (JMJDs) that require O2 and α-Ketoglutarate (α-KG) as substrates. The JMJDs affect gene expression through their regulation of the active or repressive histone methylations...
October 25, 2017: BMB Reports
Seung-Ju Yang, Jiae Kim, Sang Eun Lee, Jee-Yin Ahn, Soo Young Choi, Sung-Woo Cho
We aimed to assess the anti-inflammatory and antioxidative properties of KHG26792, a novel azetidine derivative, in amyloid β (Aβ)-treated primary microglial cells. KHG26792 attenuated the Aβ-induced production of inflammatory mediators such as IL-6, IL-1β, TNF-α, and nitric oxide. The levels of protein oxidation, lipid peroxidation, ROS, and NADHP oxidase enhanced by Aβ were also downregulated by KHG26792 treatment. The effects of KHG26792 against the Aβ-induced increases in inflammatory cytokine levels and oxidative stress were achieved by increasing the phosphorylation of Akt/GSK-3β signaling and by decreasing the Aβ-induced translocation of NF-κB...
October 25, 2017: BMB Reports
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