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lim kinase

Yuan Sheng Tao, Shang Guo Piao, Ying Shun Jin, Ji Zhe Jin, Hai Lan Zheng, Hai Yan Zhao, Sun Woo Lim, Chul Woo Yang, Can Li
BACKGROUND: Accumulating evidence suggests that a decrease in brain-derived neurotrophic factor (BDNF) level induces a variety of psychiatric and neurological disorders. However, the expression and role of BDNF in the kidney have not been explored. The present study examined the expression of BDNF and tropomyosin-related kinase (Trk) receptors in an experimental model of chronic cyclosporine A (CsA) nephropathy. METHODS: Sprague-Dawley rats on a salt-deplete diet were treated daily for four weeks with vehicle or CsA...
March 14, 2018: BMC Nephrology
Hyemi Bae, Jeongyoon Choi, Young-Won Kim, Donghee Lee, Jung-Ha Kim, Jae-Hong Ko, Hyoweon Bang, Taeho Kim, Inja Lim
This study investigated the expression of voltage-gated K⁺ (KV ) channels in human cardiac fibroblasts (HCFs), and the effect of nitric oxide (NO) on the KV currents, and the underlying phosphorylation mechanisms. In reverse transcription polymerase chain reaction, two types of KV channels were detected in HCFs: delayed rectifier K⁺ channel and transient outward K⁺ channel. In whole-cell patch-clamp technique, delayed rectifier K⁺ current (IK ) exhibited fast activation and slow inactivation, while transient outward K⁺ current (Ito ) showed fast activation and inactivation kinetics...
March 12, 2018: International Journal of Molecular Sciences
Ji-Won Park, Han-Sol Lee, Yourim Lim, Jin-Hyub Paik, Ok-Kyoung Kwon, Jung-Hee Kim, Imam Paryanto, Prasetyawan Yunianto, Sangho Choi, Sei-Ryang Oh, Kyung-Seop Ahn
Rhododendron album Blume (RA) has traditionally been used as an herbal medicine and is considered to have anti‑inflammatory properties. It is a well‑known medicine for treatment of allergic or atopic diseases. In the present study, the biological effects of an RA methanol extract (RAME) on inflammation were investigated in tumor necrosis factor‑α (TNF‑α)/interferon‑γ (IFN‑γ)‑stimulated human keratinocytes. The present study aimed to investigate the potential mechanisms by which RAME inhibited TNF‑α/IFN‑γ‑induced expression of chemokines [thymus‑ and activation-regulated chemokine (TARC) and macrophage‑derived chemokine (MDC)] and cytokines [interleukin (IL)‑6 and IL‑8] through the nuclear factor‑κB (NF‑κB) pathway in human keratinocytes...
March 9, 2018: International Journal of Molecular Medicine
Qingzu Gao, Lihua Tang, Ling Wu, Kaitao Li, Hui Wang, Weidong Li, Juan Wu, Mingyi Li, Shuang Wang, Liang Zhao
LIM and SH3 protein 1 (LASP1) enhances tumor growth and metastasis in various cancers, but its role in nasopharyngeal carcinoma (NPC) remains unclear. Herein, we investigated the role of LASP1 in NPC and explored the underlying mechanisms in NPC. Clinically, overexpression of LASP1 is associated with tumor metastasis and poor prognosis of NPC patients. Gain-of-function and loss-of-function assays showed that LASP1 promoted NPC cell proliferation, metastasis, and invasion in vitro and in vivo. Mechanistically, we observed clear co-localization between LASP1 and PTEN in NPC cells...
March 12, 2018: Cell Death & Disease
Iris Lim, Russ Chess-Williams, Donna Sellers
This study investigated the role of calcium sensitisation in the regulation of ureteral contractility with ageing. Isolated ureteral strips from young (6-month old) and older (3-year old) pigs were mounted in Krebs bicarbonate solution and contractility induced by the α1-adrenoceptor agonist phenylephrine (30 and 300 μM) and 5-HT (10 and 100 μM), recorded in the absence and presence of the rho-kinase inhibitors Y-27632 (10 μM) and fasudil (30 μM). Ureteral strips developed bursts of contractile activity which was measured as area under the curve (AUC) and frequency...
March 9, 2018: Mechanisms of Ageing and Development
Jeanie K Meckes, Patrick H Lim, Stephanie L Wert, Wendy Luo, Stephanie A Gacek, Dana Platt, Ryan Jankord, Kathrin Saar, Eva E Redei
Acute stress responsiveness is a quantitative trait that varies in severity from one individual to another; however, the genetic component underlying the individual variation is largely unknown. Fischer 344 (F344) and Wistar Kyoto (WKY) rat strains show large differences in behavioral responsiveness to acute stress, such as freezing behavior in response to footshock during the conditioning phase of contextual fear conditioning (CFC). Quantitative trait loci (QTL) have been identified for behavioral responsiveness to acute stress in the defensive burying (DB) and open field test (OFT) from a reciprocal F2 cross of F344 and WKY rat strains...
2018: PloS One
Yubao Wang, Young-Mi Li, Lukas Baitsch, Alan Huang, Yi Xiang, Haoxuan Tong, Ana Lako, Thanh Von, Christine Choi, Elgene Lim, Junxia Min, Li Li, Frank Stegmeier, Robert Schlegel, Michael J Eck, Nathanael S Gray, Timothy J Mitchison, Jean J Zhao
No abstract text is available yet for this article.
March 12, 2018: ELife
Seong Ji Park, Seung Koo Lee, Chae Rin Lim, Hye Won Park, Fang Liu, Seong-Jin Kim, Byung-Chul Kim
Heme oxygenase-1 (HO-1) has been implicated in tumor progression, but the underlying molecular mechanisms remain largely unknown. Transforming growth factor-β1 (TGF-β1) exhibits cytostatic and apoptotic effects in hepatocytes and several types of hepatocellular carcinoma (HCC) cell lines, and deregulation of its signaling pathway is linked to hepatic tumorigenesis. In the present study, we observed that HO-1 is expressed at higher levels in HCC tissues than in paired normal tissues. Moreover, TGF-β1-induced cell cycle arrest and up-regulation of cyclin-dependent kinase inhibitors in HCC cell lines were significantly attenuated by overexpression of HO-1 or treatment with tricarbonyldichlororuthenium(II) dimer ([Ru(CO)3 Cl2 ]2 , suggesting an inhibitory role of the HO-1/CO axis in TGF-β signaling to growth inhibition in HCC cell lines...
March 7, 2018: Biochemical and Biophysical Research Communications
Hok Khim Fam, Kunho Choi, Lauren Fougner, Chinten James Lim, Cornelius F Boerkoel
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a nuclear and mitochondrial protein that in nuclei and in vitro repairs blocked 3' DNA termini such as 3' phosphotyrosine conjugates resulting from stalling of topoisomerase I-DNA intermediates. Its mutation also causes spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1). Because Tdp1 colocalizes with mitochondria following oxidative stress, we hypothesized that Tdp1 repairs mitochondrial DNA (mtDNA) and that mtDNA damage mediates entry of Tdp1 into the mitochondria...
March 9, 2018: Scientific Reports
Sean P Cornillie, Benjamin J Bruno, Carol S Lim, Thomas E Cheatham
The oncogenic gene product Bcr-Abl is the principal cause of chronic myeloid leukemia (CML) and though several therapies exist to curb the aberrant kinase activity of Bcr-Abl through targeting of the Abl kinase domain, these therapies are rendered ineffective by frequent mutations in the corresponding gene. It has been demonstrated that a designed protein known as CCmut3 is able to produce a dominant negative inactivating effect on Bcr-Abl kinase by preferentially oligomerizing with the N-terminal coiled-coil oligomerization domain of Bcr-Abl (Bcr-CC) to effectively reduce the oncogenic potential of Bcr-Abl...
March 8, 2018: Journal of Physical Chemistry. B
Kee Hong Park, Patrick Waters, Mark Woodhall, Bethan Lang, Thomas Smith, Jung-Joon Sung, Kwang-Kuk Kim, Young-Min Lim, Jee-Eun Kim, Byung-Jo Kim, Jin-Sung Park, Jeong-Geon Lim, Dae-Seong Kim, Ohyun Kwon, Eun Hee Sohn, Jong Seok Bae, Byung-Nam Yoon, Nam-Hee Kim, Suk-Won Ahn, Jeeyoung Oh, Hyung Jun Park, Kyong Jin Shin, Yoon-Ho Hong
Acquired myasthenia gravis (MG) is a prototype autoimmune disease of the neuromuscular junction, caused in most patients by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). There seem to be ethnic and regional differences in the frequency and clinical features of MG seronegative for the AChR antibody. This study aimed to describe the autoantibody profiles and clinical features of Korean patients with generalized MG seronegative for the AChR antibody. A total of 62 patients with a high index of clinical suspicion of seronegative generalized MG were identified from 18 centers, and we examined their sera for antibodies to clustered AChR, muscle-specific tyrosine kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4) by cell-based assays (CBA) and to MuSK by radioimmunoprecipitation assay (RIPA)...
2018: PloS One
Mithun Ghosh, In Sook Kim, Young Min Lee, Seong Min Hong, Taek Hwan Lee, Ji Hong Lim, Trishna Debnath, Beong Ou Lim
This study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa 'Viking' (AM) and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated...
March 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Juhyun Park, Sung Yong Cho, Kwanjin Park, Ji Sun Chai, Hwancheol Son, Soo Woong Kim, Jae-Seung Paick, Min Chul Cho
We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2...
March 6, 2018: Asian Journal of Andrology
Valentina Caracciolo, Jeanette Young, Donna Gonzales, Yinchun Ni, Stephen J Flowers, Ross Summer, Scott A Waldman, Jason K Kim, Dae Young Jung, Hye Lim Noh, Taekyoon Kim, Perry J Blackshear, Danielle O'Connell, Robert C Bauer, Caleb B Kallen
Obesity is associated with adipose tissue inflammation that contributes to insulin resistance. Zinc Finger Protein 36 (Zfp36) is an mRNA-binding protein that reduces inflammation by binding to cytokine transcripts and promoting their degradation. We hypothesized that myeloid-specific deficiency of Zfp36 would lead to increased adipose tissue inflammation and reduced insulin sensitivity in diet-induced obese mice. As expected, wild type (Control) mice became obese and diabetic on a high-fat diet and obese mice with myeloid-specific loss of Zfp36 (KO) demonstrated increased adipose tissue and liver cytokine mRNA expression compared to Control mice...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Tzer Chyn Lim, Tomoyuki Hatano, Anton Kamnev, Mohan K Balasubramanian, Ting Gang Chew
The position of the division site dictates the size and fate of daughter cells in many organisms. In animal cells, division-site placement involves overlapping mechanisms, including signaling from the central spindle microtubules, astral microtubules, and spindle poles and through polar contractions [1-3]. In fission yeast, division-site positioning requires overlapping mechanisms involving the anillin-related protein Mid1 and the tip complex (comprising the Kelch-repeat protein Tea1, the Dyrk-kinase Pom1, and the SH3-domain protein Tea4) [4-11]...
February 22, 2018: Current Biology: CB
Chung Thong Lim, Márta Korbonits
Pituitary adenomas are the third most common central nervous system tumours and arise from the anterior pituitary within the pituitary fossa. The signs and symptoms of patients with pituitary adenomas vary from 'mass effects' caused by a large adenoma to features secondary to excess pituitary hormones produced by the functioning pituitary adenoma. Detailed histopathological assessment, based on novel classifications and the latest WHO guidelines, helps to categorise pituitary adenomas into different subtypes and identify features that, in some cases, help to predict their behaviour...
March 2, 2018: Endocrine Practice
Haet Nim Lim, Jun-Pil Jang, Jang Mi Han, Jae-Hyuk Jang, Jong Seog Ahn, Hye Jin Jung
Angiogenesis plays a very important role in tumor progression through the creation of new blood vessels. Therefore, angiogenesis inhibitors could contribute to cancer treatment. Here, we show that a microbial metabolite, elaiophylin, exhibits potent antiangiogenic activity from in vitro and in vivo angiogenesis assays. Elaiophylin dramatically suppressed in vitro angiogenic characteristics such as proliferation, migration, adhesion, invasion and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated by vascular endothelial growth factor (VEGF) at non-toxic concentrations...
March 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ae Lee Jeong, Hye In Ka, Sora Han, Sunyi Lee, Eun-Woo Lee, Su Jung Soh, Hyun Jeong Joo, Buyanravjkh Sumiyasuren, Ji Young Park, Jong-Seok Lim, Jong Hoon Park, Myung Sok Lee, Young Yang
In most mammalian cells, the primary cilium is a microtubule-enriched protrusion of the plasma membrane and acts as a key coordinator of signaling pathways during development and tissue homeostasis. The primary cilium is generated from the basal body, and cancerous inhibitor of protein phosphatase 2A (CIP2A), the overexpression of which stabilizes c-MYC to support the malignant growth of tumor cells, is localized in the centrosome. Here, we show that CIP2A overexpression induces primary cilia disassembly through the activation of Aurora A kinase, and CIP2A depletion increases ciliated cells and cilia length in retinal pigment epithelium (RPE1) cells...
February 28, 2018: EMBO Reports
Tatyana Zykova, Feng Zhu, Lei Wang, Haitao Li, Do Young Lim, Ke Yao, Eunmiri Roh, Sang-Pil Yoon, Hong-Gyum Kim, Ki Beom Bae, Weihong Wen, Seung Ho Shin, Janos Nadas, Yan Li, Weiya Ma, Ann M Bode, Zigang Dong
The biological functions of the p53 related protein kinase (PRPK) remain unclear. We have previously demonstrated that PRPK is phosphorylated by the T-LAK cell-originated protein kinase (TOPK) and that phosphorylated PRPK (p-PRPK) promotes colon cancer metastasis. Here, we analyzed colon adenocarcinomas from 87 patients, and found that higher expression levels of p-PRPK were associated with later stages of metastatic dissemination (stages III or IV), as compared to earlier stages (stages I and II). Indeed, levels of p-PRPK were higher in metastatic versus malignant human colon adenocarcinomas...
February 26, 2018: Molecular Cancer Therapeutics
Sun Min Lim, Nicholas L Syn, Byoung Chul Cho, Ross A Soo
The tyrosine kinase inhibitors (TKIs) directed at sensitizing mutations in the epidermal growth factor receptor (EGFR) gene represents a critical pillar in non-small cell lung cancer treatment. Despite the excellent disease control with initial EGFR TKI therapy, acquired resistance is ubiquitous and remains a key challenge. Investigations into the mechanisms which foster resistance to EGFR TKIs has led to the discovery of novel biomarkers and drug targets, and in turn has enabled the development of third-generation TKIs and proposals for rational therapeutic combinations...
February 20, 2018: Cancer Treatment Reviews
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