Go to the main menu
Skip to content
Go to bottom
REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Molecules and Cells
Journal Basic Information
Journal DOI :
Korea Society for Molecular and Cellular Biology
Editor in Chief :
Volume & Issues
Volume 37, Issue 11 - Nov 2014
Volume 37, Issue 10 - Oct 2014
Volume 37, Issue 9 - Sep 2014
Volume 37, Issue 8 - Aug 2014
Volume 37, Issue 7 - Jul 2014
Volume 37, Issue 6 - Jun 2014
Volume 37, Issue 5 - May 2014
Volume 37, Issue 4 - Apr 2014
Volume 37, Issue 3 - Mar 2014
Volume 37, Issue 2 - Feb 2014
Volume 37, Issue 1 - Jan 2014
Selecting the target year
NF-κB in Cellular Senescence and Cancer Treatment
Jing, Hua ; Lee, Soyoung ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 189~195
DOI : 10.14348/molcells.2014.2353
pathway transcriptionally controls a large set of target genes that play important roles in cell survival, inflammation, and immune responses. While many studies showed anti-tumorigenic and pro-survival role of NF-
in cancer cells, recent findings postulate that NF-
participates in a senescence-associated cytokine response, thereby suggesting a tumor restraining role of NF-
. In this review, we discuss implications of the NF-
signaling pathway in cancer. Particularly, we emphasize the connection of NF-
with cellular senescence as a response to chemotherapy, and furthermore, present examples how distinct oncogenic network contexts surrounding NF-
produce fundamentally different treatment outcomes in aggressive B-cell lymphomas as an example.
Apelin-APJ Signaling: a Potential Therapeutic Target for Pulmonary Arterial Hypertension
Kim, Jongmin ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 196~201
DOI : 10.14348/molcells.2014.2308
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by the vascular remodeling of the pulmonary arterioles, including formation of plexiform and concentric lesions comprised of proliferative vascular cells. Clinically, PAH leads to increased pulmonary arterial pressure and subsequent right ventricular failure. Existing therapies have improved the outcome but mortality still remains exceedingly high. There is emerging evidence that the seven-transmembrane G-protein coupled receptor APJ and its cognate endogenous ligand apelin are important in the maintenance of pulmonary vascular homeostasis through the targeting of critical mediators, such as Kr
ppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and microRNAs (miRNAs). Disruption of this pathway plays a major part in the pathogenesis of PAH. Given its role in the maintenance of pulmonary vascular homeostasis, the apelin-APJ pathway is a potential target for PAH therapy. This review highlights the current state in the understanding of the apelin-APJ axis related to PAH and discusses the therapeutic potential of this signaling pathway as a novel paradigm of PAH therapy.
Electrophysiological Characteristics of Six Mutations in hClC-1 of Korean Patients with Myotonia Congenita
Ha, Kotdaji ; Kim, Sung-Young ; Hong, Chansik ; Myeong, Jongyun ; Shin, Jin-Hong ; Kim, Dae-Seong ; Jeon, Ju-Hong ; So, Insuk ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 202~212
DOI : 10.14348/molcells.2014.2267
ClC-1 is a member of a large family of voltage-gated chloride channels, abundantly expressed in human skeletal muscle. Mutations in ClC-1 are associated with myotonia congenita (MC) and result in loss of regulation of membrane excitability in skeletal muscle. We studied the electrophysiological characteristics of six mutants found among Korean MC patients, using patch clamp methods in HEK293 cells. Here, we found that the autosomal dominant mutants S189C and P480S displayed reduced chloride conductances compared to WT. Autosomal recessive mutant M128I did not show a typical rapid deactivation of Cl- currents. While sporadic mutant G523D displayed sustained activation of
currents in the whole cell traces, the other sporadic mutants, M373L and M609K, demonstrated rapid deactivations.
of these mutants was shifted to more depolarizing potentials. In order to identify potential effects on gating processes, slow and fast gating was analyzed for each mutant. We show that slow gating of the mutants tends to be shifted toward more positive potentials in comparison to WT. Collectively, these six mutants found among Korean patients demonstrated modifications of channel gating behaviors and reduced chloride conductances that likely contribute to the physiologic changes of MC.
The Up-Regulation of miR-199b-5p in Erythroid Differentiation Is Associated with GATA-1 and NF-E2
Li, Yuxia ; Bai, Hua ; Zhang, Zhongzu ; li, Weihua ; Dong, Lei ; Wei, Xueju ; Ma, Yanni ; Zhang, Junwu ; Yu, Jia ; Sun, Guotao ; Wang, Fang ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 213~219
DOI : 10.14348/molcells.2014.2288
MicroRNAs (miRNAs) represent a class of small non-coding regulatory RNAs that play important roles in normal hematopoiesis, including erythropoiesis. Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. In this study, we identified miR-199b-5p as a key regulator of human erythropoiesis, and its expression was up-regulated during the erythroid differentiation of K562 cells. Furthermore, the increase of miR-199b-5p in erythroid cells occurred in a GATA-1- and NF-E2-dependent manner during erythrocyte maturation. Both GATA-1 and NF-E2 bound upstream of the miR-199b gene locus and activated its transcription. Forced expression of miRNA-199b-5p in K562 cells affected erythroid cell proliferation and maturation. Moreover, we identified c-Kit as a direct target of miR-199b-5p in erythroid cells. Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation.
PV.1 Suppresses the Expression of FoxD5b during Neural Induction in Xenopus Embryos
Yoon, Jaeho ; Kim, Jung-Ho ; Kim, Sung Chan ; Park, Jae-Bong ; Lee, Jae-Yong ; Kim, Jaebong ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 220~225
DOI : 10.14348/molcells.2014.2302
Suppression of bone morphogenetic protein (BMP) signaling induces neural induction in the ectoderm of developing embryos. BMP signaling inhibits neural induction via the expression of various neural suppressors. Previous research has demonstrated that the ectopic expression of dominant negative BMP receptors (DNBR) reduces the expression of target genes down-stream of BMP and leads to neural induction. Additionally, gain-of-function experiments have shown that BMP downstream target genes such as MSX1, GATA1b and Vent are involved in the suppression of neural induction. For example, the Vent1/2 genes are involved in the suppression of Geminin and Sox3 expression in the neural ectodermal region of embryos. In this paper, we investigated whether PV.1, a BMP downstream target gene, negatively regulates the expression of FoxD5b, which plays a role in maintaining a neural progenitor population. A promoter assay and a cyclohexamide experiment demonstrated that PV.1 negatively regulates FoxD5b expression.
Tat-Fused Recombinant Human SAG Prevents Dopaminergic Neurodegeneration in a MPTP-Induced Parkinson`s Disease Model
Sohn, Eun Jeong ; Shin, Min Jea ; Kim, Dae Won ; Ahn, Eun Hee ; Jo, Hyo Sang ; Kim, Duk-Soo ; Cho, Sung-Woo ; Han, Kyu Hyung ; Park, Jinseu ; Eum, Won Sik ; Hwang, Hyun Sook ; Choi, Soo Young ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 226~233
DOI : 10.14348/molcells.2014.2314
Excessive reactive oxygen species (ROS) generated from abnormal cellular process lead to various human diseases such as inflammation, ischemia, and Parkinson`s disease (PD). Sensitive to apoptosis gene (SAG), a RING-FINGER protein, has anti-apoptotic activity and anti-oxidant activity. In this study, we investigate whether Tat-SAG, fused with a Tat domain, could protect SH-SY5Y neuroblastoma cells against 1-methyl-4-phenylpyridinium (
) and dopaminergic (DA) neurons in the substantia nigra (SN) against 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) toxicity. Western blot and immunohistochemical analysis showed that, unlike SAG, Tat-SAG transduced efficiently into SH-SY5Y cells and into the brain, respectively. Tat-SAG remarkably suppressed ROS generation, DNA damage, and the progression of apoptosis, caused by
in SH-SY5Y cells. Also, immunohistochemical data using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that Tat-SAG obviously protected DA neurons in the SN against MPTP toxicity in a PD mouse model. Tat-SAG-treated mice showed significant enhanced motor activities, compared to SAG- or Tat-treated mice. Therefore, our results suggest that Tat-SAG has potential as a therapeutic agent against ROS-related diseases such as PD.
Capsaicin Ameliorates Cisplatin-Induced Renal Injury through Induction of Heme Oxygenase-1
Jung, Sung-Hyun ; Kim, Hyung-Jin ; Oh, Gi-Su ; Shen, AiHua ; Lee, Subin ; Choe, Seong-Kyu ; Park, Raekil ; So, Hong-Seob ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 234~240
DOI : 10.14348/molcells.2014.2322
Cisplatin is one of the most potent chemotherapy agents. However, its use is limited due to its toxicity in normal tissues, including the kidney and ear. In particular, nephrotoxicity induced by cisplatin is closely associated with oxidative stress and inflammation. Heme oxygenase-1(HO-1), the rate-limiting enzyme in the heme metabolism, has been implicated in a various cellular processes, such as inflammatory injury and anti-oxidant/oxidant homeostasis. Capsaicin is reported to have therapeutic potential in cisplatin-induced renal failures. However, the mechanisms underlying its protective effects on cisplatin-induced nephrotoxicity remain largely unknown. Herein, we demonstrated that administration of capsaicin ameliorates cisplatin-induced renal dysfunction by assessing the levels of serum creatinine and blood urea nitrogen (BUN) as well as tissue histology. In addition, capsaicin treatment attenuates the expression of inflammatory mediators and oxidative stress markers for renal damage. We also found that capsaicin induces HO-1 expression in kidney tissues and HK-2 cells. Notably, the protective effects of capsaicin were completely abrogated by treatment with either the HO inhibitor ZnPP IX or HO-1 knockdown in HK-2 cells. These results suggest that capsaicin has protective effects against cisplatin-induced renal dysfunction through induction of HO-1 as well as inhibition oxidative stress and inflammation.
Postmortem mRNA Expression Patterns in Left Ventricular Myocardial Tissues and Their Implications for Forensic Diagnosis of Sudden Cardiac Death
Son, Gi Hoon ; Park, Seong Hwan ; Kim, Yunmi ; Kim, Ji Yeon ; Kim, Jin Wook ; Chung, Sooyoung ; Kim, Yu-Hoon ; Kim, Hyun ; Hwang, Juck-Joon ; Seo, Joong-Seok ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 241~247
DOI : 10.14348/molcells.2014.2344
Sudden cardiac death (SCD), which is primarily caused by lethal heart disorders resulting in structural and arrhythmogenic abnormalities, is one of the prevalent modes of death in most developed countries. Myocardial ischemia, mainly due to coronary artery disease, is the most common type of heart disease leading to SCD. However, postmortem diagnosis of SCD is frequently complicated by obscure histological evidence. Here, we show that certain mRNA species, namely those encoding hemoglobin A1/2 and B (Hba1/2 and Hbb, respectively) as well as pyruvate dehydrogenase kinase 4 (Pdk4), exhibit distinct postmortem expression patterns in the left ventricular free wall of SCD subjects when compared with their expression patterns in the corresponding tissues from control subjects with non-cardiac causes of death. Hba1/2 and Hbb mRNA expression levels were higher in ischemic SCD cases with acute myocardial infarction or ischemic heart disease without recent infarction, and even in cardiac death subjects without apparent pathological signs of heart injuries, than control subjects. By contrast, Pdk4 mRNA was expressed at lower levels in SCD subjects. In conclusion, we found that altered myocardial Hba1/2, Hbb, and Pdk4 mRNA expression patterns can be employed as molecular signatures of fatal cardiac dysfunction to forensically implicate SCD as the primary cause of death.
The Non-Canonical Effect of N-Acetyl-D-Glucosamine Kinase on the Formation of Neuronal Dendrites
Lee, HyunSook ; Cho, Sun-Jung ; Moon, Il Soo ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 248~256
DOI : 10.14348/molcells.2014.2354
N-acetylglucosamine kinase (GlcNAc kinase or NAGK; EC 220.127.116.11) is a N-acetylhexosamine kinase that belong to the sugar kinase/heat shock protein 70/actin superfamily. In this study, we investigated both the expression and function of NAGK in neurons. Immunohistochemistry of rat brain sections showed that NAGK was expressed at high levels in neurons but at low levels in astrocytes. Immunocytochemistry of rat hippocampal dissociate cultures confirmed these findings and showed that NAGK was also expressed at low levels in oligodendrocytes. Furthermore, several NAGK clusters were observed in the nucleoplasm of both neuron and glia. The overexpression of EGFP- or RFP (DsRed2)-tagged NAGK in rat hippocampal neurons (DIV 5-9) increased the complexity of dendritic architecture by increasing the numbers of primary dendrites and dendritic branches. In contrast, knockdown of NAGK by shRNA resulted in dendrite degeneration, and this was prevented by the co-expression of RFP-tagged NAGK. These results suggest that the upregulation of dendritic complexity is a non-canonical function of NAGK.
Transient Receptor Potential Cation Channel V1 (TRPV1) Is Degraded by Starvation- and Glucocorticoid-Mediated Autophagy
Ahn, Seyoung ; Park, Jungyun ; An, Inkyung ; Jung, Sung Jun ; Hwang, Jungwook ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 257~263
DOI : 10.14348/molcells.2014.2384
A mammalian cell renovates itself by autophagy, a process through which cellular components are recycled to produce energy and maintain homeostasis. Recently, the abundance of gap junction proteins was shown to be regulated by autophagy during starvation conditions, suggesting that transmembrane proteins are also regulated by autophagy. Transient receptor potential vanilloid type 1 (TRPV1), an ion channel localized to the plasma membrane and endoplasmic reticulum (ER), is a sensory transducer that is activated by a wide variety of exogenous and endogenous physical and chemical stimuli. Intriguingly, the abundance of cellular TRPV1 can change dynamically under pathological conditions. However, the mechanisms by which the protein levels of TRPV1 are regulated have not yet been explored. Therefore, we investigated the mechanisms of TRPV1 recycling using HeLa cells constitutively expressing TRPV1. Endogenous TRPV1 was degraded in starvation conditions; this degradation was blocked by chloroquine (CLQ), 3MA, or downregulation of Atg7. Interestingly, a glucocorticoid (cortisol) was capable of inducing autophagy in HeLa cells. Cortisol increased cellular conversion of LC3-I to LC-3II, leading autophagy and resulting in TRPV1 degradation, which was similarly inhibited by treatment with CLQ, 3MA, or downregulation of Atg7. Furthermore, cortisol treatment induced the colocalization of GFP-LC3 with endogenous TRPV1. Cumulatively, these observations provide evidence that degradation of TRPV1 is mediated by autophagy, and that this pathway can be enhanced by cortisol.
A Conserved Mechanism for Binding of p53 DNA-Binding Domain and Anti-Apoptotic Bcl-2 Family Proteins
Lee, Dong-Hwa ; Ha, Ji-Hyang ; Kim, Yul ; Jang, Mi ; Park, Sung Jean ; Yoon, Ho Sup ; Kim, Eun-Hee ; Bae, Kwang-Hee ; Park, Byoung Chul ; Park, Sung Goo ; Yi, Gwan-Su ; Chi, Seung-Wook ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 264~269
DOI : 10.14348/molcells.2014.0001
The molecular interaction between tumor suppressor p53 and the anti-apoptotic Bcl-2 family proteins plays an essential role in the transcription-independent apoptotic pathway of p53. In this study, we investigated the binding of p53 DNA-binding domain (p53DBD) with the anti-apoptotic Bcl-2 family proteins, Bcl-w, Mcl-1, and Bcl-2, using GST pull-down assay and NMR spectroscopy. The GST pull-down assays and NMR experiments demonstrated the direct binding of the p53DBD with Bcl-w, Mcl-1, and Bcl-2. Further, NMR chemical shift perturbation data showed that Bcl-w and Mcl-1 bind to the positively charged DNA-binding surface of p53DBD. Noticeably, the refined structural models of the complexes between p53DBD and Bcl-w, Mcl-1, and Bcl-2 showed that the binding mode of p53DBD is highly conserved among the anti-apoptotic Bcl-2 family proteins. Furthermore, the chemical shift perturbations on Bcl-w, Mcl-1, and Bcl-2 induced by p53DBD binding occurred not only at the p53DBD-binding acidic region but also at the BH3 peptide-binding pocket, which suggests an allosteric conformational change similar to that observed in Bcl-
. Taken altogether, our results revealed a structural basis for a conserved binding mechanism between p53DBD and the anti-apoptotic Bcl-2 family proteins, which shed light on to the molecular understanding of the transcription-independent apoptosis pathway of p53.
Alk3/Alk3b and Smad5 Mediate BMP Signaling during Lymphatic Development in Zebrafish
Kim, Jun-Dae ; Kim, Jongmin ;
Molecules and Cells, volume 37, issue 3, 2014, Pages 270~274
DOI : 10.14348/molcells.2014.0005
Lymphatic vessels are essential to regulate interstitial fluid homeostasis and diverse immune responses. A number of crucial factors, such as VEGFC, SOX18, PROX1, FOX2C, and GJC2, have been implicated in differentiation and/or maintenance of lymphatic endothelial cells (LECs). In humans, dysregulation of these genes is known to cause lymphedema, a debilitating condition which adversely impacts the quality of life of affected individuals. However, there are no currently available pharmacological treatments for lymphedema, necessitating identification of additional factors modulating lymphatic development and function which can be targeted for therapy. In this report, we investigate the function of genes associated with Bone Morphogenetic Protein (BMP) signaling in lymphatic development using zebrafish embryos. The knock-down of BMP type II receptors, Bmpr2a and Bmpr2b, and type I receptors, Alk3 and Alk3b, as well as SMAD5, an essential cellular mediator of BMP signaling, led to distinct lymphatic defects in developing zebrafish. Therefore, it appears that each constituent of the BMP signaling pathway may have a unique function during lymphatic development. Taken together, our data demonstrate that BMP signaling is essential for normal lymphatic vessel development in zebrafish.