Hua Jing, and Soyoung LeeMol. Cells 2014; 37(3): 189-195 https://doi.org/10.14348/molcells.2014.2353
Abstract : The NF-κB 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-κB in cancer cells, recent findings postulate that NF-κB participates in a senescence-associated cytokine response, thereby suggesting a tumor restraining role of NF-κB. In this review, we discuss implications of the NF-κB signaling pathway in cancer. Particularly, we emphasize the connection of NF-κB with cellular senescence as a response to chemotherapy, and furthermore, present examples how distinct oncogenic network contexts surrounding NF-κB produce fundamentally different treatment outcomes in aggressive B-cell lymphomas as an example.
Jongmin KimMol. Cells 2014; 37(3): 196-201 https://doi.org/10.14348/molcells.2014.2308
Abstract : 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.
Kotdaji Ha, Sung-Young Kim, Chansik Hong, Jongyun Myeong, Jin-Hong Shin, Dae-Seong Kim, Ju-Hong Jeon, and Insuk SoMol. Cells 2014; 37(3): 202-212 https://doi.org/10.14348/molcells.2014.2267
Abstract : 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 Cl? currents in the whole cell traces, the other sporadic mutants, M373L and M609K, demonstrated rapid deactivations. V1/2 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.
Yuxia Li, Hua Bai, Zhongzu Zhang, Weihua li, Lei Dong, Xueju Wei, Yanni Ma, Junwu Zhang, Jia Yu, Guotao Sun, and Fang WangMol. Cells 2014; 37(3): 213-219 https://doi.org/10.14348/molcells.2014.2288
Abstract : 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
Jaeho Yoon, Jung-Ho Kim, Sung Chan Kim, Jae-Bong Park, Jae-Yong Lee, and Jaebong KimMol. Cells 2014; 37(3): 220-225 https://doi.org/10.14348/molcells.2014.2302
Abstract : Suppression of bone morphogenetic protein (BMP) signaling induces neural induction in the ectoderm of developing embryos. BMP signaling inhibits eural induction
Eun Jeong Sohn, Min Jea Shin, Dae Won Kim, Eun Hee Ahn, Hyo Sang Jo, Duk-Soo Kim, Sung-Woo Cho, Kyu Hyung Han, Jinseu Park, Won Sik Eum, Hyun Sook Hwang, and Soo Young ChoiMol. Cells 2014; 37(3): 226-233 https://doi.org/10.14348/molcells.2014.2314
Abstract : 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 (MPP+) and dopaminergic (DA) neurons in the substantia nigra (SN) against 1-methyl-4-phenyl-1,2,3,6-
Sung-Hyun Jung, Hyung-Jin Kim, Gi-Su Oh, AiHua Shen, Subin Lee, Seong-Kyu Choe, Raekil Park, and Hong-Seob SoMol. Cells 2014; 37(3): 234-240 https://doi.org/10.14348/molcells.2014.2322
Abstract : 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.
Gi Hoon Son, Seong Hwan Park, Yunmi Kim, Ji Yeon Kim, Jin Wook Kim, Sooyoung Chung, Yu-Hoon Kim, Hyun Kim, Juck-Joon Hwang, and Joong-Seok SeoMol. Cells 2014; 37(3): 241-247 https://doi.org/10.14348/molcells.2014.2344
Abstract : 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 (
HyunSook Lee, Sun-Jung Cho, and Il Soo MoonMol. Cells 2014; 37(3): 248-256 https://doi.org/10.14348/molcells.2014.2354
Seyoung Ahn, Jungyun Park, Inkyung An, Sung Jun Jung, and Jungwook HwangMol. Cells 2014; 37(3): 257-263 https://doi.org/10.14348/molcells.2014.2384
Abstract : 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.