자기력 기술을 이용한 렛풀다운 단축성 웨이트 기구와 고전적 렛풀다운 웨이트 기구의 근전도 비교

최대혁,소위영,김수미 한국웰니스학회 2013 한국웰니스학회지 Vol.8 No.1

본 연구의 목적은 자기력 기술을 이용한 렛풀다운 단축성 웨이트 트레이닝 기구와 고전적 렛풀다운 웨이트 트레이닝 기구의 근육활성화 비율(근전도)을 비교하는데 있다. 연구대상자는 20대의 건강하고, 의학적으로 특별한 질환이 없는 남자대학생 20명으로 구성되었다. 연구대상자들은 자기력 기술을 이용한 단축성 렛풀다운 운동기구와 단축성과 신장성 운동형태를 모두 포함한 고전적 렛풀다운 운동기구를 수행하여 근전도를 측정하였다. 근피로에 의한 간섭을 배제하기 위하여 자기력 기술을 이용한 렛풀다운 기구와 고전적 렛풀다운 기구의 순서를 바꾸어 가면서 측정하였고, 측정은 굴곡과 신전을 1회로 하여 5회 동작으로 실시하였으며, 각 시도에 2분 동안의 동일한 휴식을 제공하여 총 측정횟수는 20명 X 5회로 구성되었으며 총 100회의 측정값이 분석에 사용되었다. 이두근에서의 근전도 활성비율의 결과 자기력 기술을 이용한 단축성 렛풀다운은 68.63 ± 60.19%, 고전적 렛풀다운은 91.65 ± 69.32%로 집단 간의 유의한 차이가 나타났다(p=0.013). 삼두근에서의 근전도 활성비율의 결과 자기력 기술을 이용한 단축성 렛풀다운은 90.90 ± 89.35%, 고전적 렛풀다운은 140.13 ± 136.97%로 집단 간의 유의한 차이가 나타났다(p=0.003). 후삼각근에서의 근전도 활성비율의 결과 자기력 기술을 이용한 단축성 렛풀다운은 188.76 ± 190.90%, 고전적 렛풀다운은 377.17 ± 327.20%로 집단 간의 유의한 차이가 나타났다(p<0.001). 광배근에서의 근전도 활성비율의 결과 자기력 기술을 이용한 단축성 렛풀다운은 145.19 ± 88.06%, 고전적 렛풀다운은 236.84 ± 138.32%로 집단 간의 유의한 차이가 나타났다(p<0.001). 전거근에서의 근전도 활성비율의 결과 자기력 기술을 이용한 단축성 렛풀다운은 56.64 ± 33.02%, 고전적 렛풀다운은 81.78 ± 45.27%로 집단 간의 유의한 차이가 나타났다(p<0.001). 본 연구결과를 통하여 자기력 기술을 이용한 단축성 웨이트 트레이닝 기구는 근육활성화 비율이 통계적으로 낮게 나타났으며, 이는 운동 후에 나타나는 근손상을 예방하여 만성근육통을 방지할 수 있는 새로운 운동형태가 될 수 있을 것이라 사료된다. The purpose of this study was to compare the ratio of the electromyograms (EMGs) obtained while using concentric lat-pull down weight-training machines based on magnetic technology and traditional lat-pull down weight-training machines. The subjects were physically and psychologically healthy 20 university students who were aged between 21 and 28. EMGs were obtained while the subjects performed lat-pull downs using a magnetic skilled concentric weight-training machine and a classical concentric?eccentric weight-training machine. One repetition was defined as 1 flexion and 1 extension. Each subject randomly performed 5 repetitions of the magnetic skilled concentric lat-pull down, followed by a 2-minute rest, and then 5 repetitions of classical concentric?eccentric lat-pull downs. Thus, we analyzed total 100 repetitions (20 subjects × 5 repetitions) of each type. Ratios of EMGs of the biceps muscle showed significant difference, magnetic lat-pull down with 68.63 ± 60.19% and classical lat-pull down with 91.65 ± 69.32% (p = 0.013). Similarly, ratios of EMGs of the triceps muscle significantly different, magnetic lat-pull down with 90.90 ± 89.35% and classical lat-pull down with 140.13 ± 136.97% (p = 0.003). Significant difference was also observed in the ratio of EMGs of the posterior deltoid muscle, magnetic lat-pull down with 188.76 ± 190.90% and classical lat-pull down with 377.17 ± 327.20% (p < 0.001). In addition, a significant difference was observed in the ratio of EMGs of the latissimus dorsi muscle, magnetic lat-pull down with 145.19 ± 88.06% and classical lat-pull down with 236.84 ± 138.32% (p < 0.001). Finally, a significant difference was observed in the ratio of the EMGs of the serratus anterior muscle, magnetic lat-pull down with 56.64 ± 33.02% and classical lat-pull down with 81.78 ± 45.27% (p < 0.001). On the basis of these results, we concluded that the magnetic skilled concentric weight-training machine could be used as a new type of fitness equipment for prevention of muscle damage.

Clinicopathological Significance of Large Tumor Suppressor (LATS) Expression in Gastric Cancer

Son, Myoung Won,Song, Geum Jong,Jang, Si-Hyong,Hong, Soon Auck,Oh, Mee-Hye,Lee, Ji-Hye,Baek, Moo Jun,Lee, Moon Soo The Korean Gastric Cancer Association 2017 Journal of gastric cancer Vol.17 No.4

Purpose: The aims of this study were to evaluate the expression of the large tumor suppressor (LATS) genes LATS1 and LATS2 by immunohistochemical staining of gastric cancer, and to evaluate the clinicopathological significance of LATS expression and its correlation with overall survival (OS). Materials and Methods: LATS1 and LATS2 expression in a tissue microarray was detected by immunohistochemistry, using 264 gastric cancer specimens surgically resected between July 2006 and December 2009. Results: Low expression of LATS1 was significantly associated with more advanced American Joint Committee on Cancer (AJCC) stage (P=0.001) and T stage (P=0.032), lymph node (LN) metastasis (P=0.040), perineural invasion (P=0.042), poor histologic grade (P=0.007), and diffuse-type histology by the Lauren classification (P=0.033). Low expression of LATS2 was significantly correlated with older age (${\geq}65$, P=0.027), more advanced AJCC stage (P=0.001) and T stage (P=0.001), LN metastasis (P=0.004), perineural invasion (P=0.004), poor histologic grade (P<0.001), and diffuse-type histology by the Lauren classification (P<0.001). Kaplan-Meier survival analysis revealed significantly poor OS rates in the groups with low LATS1 (P=0.037) and LATS2 (P=0.037) expression. Conclusions: Expression of LATS1 or LATS2 is a significant marker for a good prognosis in patients with gastric cancer.

Clinicopathological Significance of Large Tumor Suppressor (LATS) Expression in Gastric Cancer

손명원,송금종,장시형,홍순억,오미혜,이지혜,백무준,이문수 대한위암학회 2017 Journal of gastric cancer Vol.17 No.4

Purpose: The aims of this study were to evaluate the expression of the large tumor suppressor (LATS) genes LATS1 and LATS2 by immunohistochemical staining of gastric cancer, and to evaluate the clinicopathological significance of LATS expression and its correlation with overall survival (OS). Materials and Methods: LATS1 and LATS2 expression in a tissue microarray was detected by immunohistochemistry, using 264 gastric cancer specimens surgically resected between July 2006 and December 2009. Results: Low expression of LATS1 was significantly associated with more advanced American Joint Committee on Cancer (AJCC) stage (P=0.001) and T stage (P=0.032), lymph node (LN) metastasis (P=0.040), perineural invasion (P=0.042), poor histologic grade (P=0.007), and diffuse-type histology by the Lauren classification (P=0.033). Low expression of LATS2 was significantly correlated with older age (≥65, P=0.027), more advanced AJCC stage (P=0.001) and T stage (P=0.001), LN metastasis (P=0.004), perineural invasion (P=0.004), poor histologic grade (P<0.001), and diffuse-type histology by the Lauren classification (P<0.001). Kaplan-Meier survival analysis revealed significantly poor OS rates in the groups with low LATS1 (P=0.037) and LATS2 (P=0.037) expression. Conclusions: Expression of LATS1 or LATS2 is a significant marker for a good prognosis in patients with gastric cancer.

아미노산 수송체 LAT1 RNA interference에 의한 사람 구강편평세포암종 KB 세포의 성장억제

김창현,홍주영,양준기,조현우,김지혜,홍민기,신용우,김도경 대한구강악안면병리학회 2006 대한구강악안면병리학회지 Vol.30 No.1

Amino acid transporters are essential for the growth and proliferation in all living cells. Among the amino acid transporters, the system L amino acid transporters are the major nutrient transport system responsible for the Na+-independent transport of neutral amino acids including several essential amino acids. The L-type amino acid transporter 1 (LAT1) is over-expressed to support cell growth in malignant tumors. The double stranded RNA-mediated RNA interference (RNAi) analysis can be in a wide variety of eukaryotes to induce the sequence-specific inhibition of gene expression. In this study, we examined the effect of LAT1 short interfering RNA (siRNA) on cell growth using siRNA of LAT1 in the KB human oral squamous cell carcinoma. In the RT-PCR analysis and western blot analysis, the siRNA of LAT1 inhibited expressions of LAT1 mRNA and protein. The uptake of [14C]L-leucine was inhibited by siRNA of LAT1. In the MTT assay, the siRNA of LAT1 inhibited the growth of the KB cells in the time-dependent manner, indicating that the growth inhibition of KB cell by the siRNA of LAT1 is induced by the blocking of neutral amino acid transport mediated by LAT1. These results suggest that the transport of neutral amino acids including several essential amino acids into the KB human oral squamous cell carcinoma is mediated mainly by LAT1. Further, the LAT1 would be a new target for the inhibition of cancer cell growth.

Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression

Liang, Zhongxing,Cho, Heidi T.,Williams, Larry,Zhu, Aizhi,Liang, Ke,Huang, Ke,Wu, Hui,Jiang, Chunsu,Hong, Samuel,Crowe, Ronald,Goodman, Mark M.,Shim, Hyun-Suk The Korea Society of Nuclear Medicine 2011 핵의학 분자영상 Vol.45 No.2

Purpose L-type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer. Methods LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with anti-1-amino-3-[$^{18}F$]fluorocyclobutane-1-carboxylic acid (anti-[$^{18}F$]FACBC) PET was assessed for its diagnostic biomarker potential. Results Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high-grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced-stage breast cancer. Furthermore, the blockade of LAT1 with its inhibitor, 2-aminobicyclo[ 2.2.1]heptane-2-carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, anti-[$^{18}F$]FACBC, has been demonstrated to be an excellent PET tracer for the non-invasive imaging of malignant breast cancer using an orthotopic animal model. Conclusions The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. Anti-[$^{18}F$]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging.

Hypermethylation of Promoter Region of LATS1 - a CDK Interacting Protein in Oral Squamous Cell Carcinomas - a Pilot Study in India

Reddy, Vijaya Ramakrishna,Annamalai, Thangavelu,Narayanan, Vivek,Ramanathan, Arvind Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.4

Background: Epigenetic silencing of tumor suppressor genes due to promoter hypermethylation is one of the frequent mechanisms observed in cancers. Hypermethylation of several tumor suppressor genes involved in cell cycle regulation has been reported in many types of tumors including oral squamous cell carcinomas. LATS1 (Large Tumor Suppressor, isoform 1) is a novel tumor suppressor gene that regulates cell cycle progression by forming complexes with the cyclin dependent kinase, CDK1. Promoter hypermethylation of the LATS1 gene has been observed in several carcinomas and also has been linked with prognosis. However, the methylation status of LATS1 in oral squamous cell carcinomas is not known. As oral cancer is one of the most prevalent forms of cancer in India, the present study was designed to investigate the methylation status of LATS1 promoter and associate it with histopathological findings in order to determine any associations of the genetic status with stage of differentiation. Materials and Methods: Tumor chromosomal DNA isolated from biopsy tissues of thirteen oral squamous cell carcinoma biopsy tissues were subjected to digestion with methylation sensitive HpaII enzyme followed by amplification with primers flanking CCGG motifs in promoter region of LATS1 gene. The PCR amplicons were subsequently subjected to agarose gel electrophoresis along with undigested amplification control. Results: HpaII enzyme based methylation sensitive PCR identified LATS1 promoter hypermethylation in seven out of thirteen oral squamous cell carcinoma samples. Conclusions: The identification of LATS1 promoter hypermethylation in seven oral squamous cell carcinoma samples (54%), which included one sample with epithelial dysplasia, two early invasive and one moderately differentiated lesions indicates that the hypermethylation of this gene may be one of the early event during carcinogenesis. To the best of our knowledge, this is the first study to have explored and identified positive association between LATS1 promoter hypermethylation with histopathological features in oral squamous cell carcinomas.

Hippo signaling is intrinsically regulated during cell cycle progression by APC/C^Cdh1

Kim, Wantae,Cho, Yong Suk,Wang, Xiaohui,Park, Ogyi,Ma, Xueyan,Kim, Hanjun,Gan, Wenjian,Jho, Eek-hoon,Cha, Boksik,Jeung, Yun-ji,Zhang, Lei,Gao, Bin,Wei, Wenyi,Jiang, Jin,Chung, Kyung-Sook,Yang, Yingzi National Academy of Sciences 2019 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.116 No.19

<P><B>Significance</B></P><P>The Hippo signaling pathway is evolutionarily conserved in the animal kingdom and plays essential roles in regulating tissue growth during development and regeneration. We have identified APC/C<SUP>Cdh1</SUP>, a core component of cell cycle control machinery, as an evolutionarily conserved and previously unknown regulator of large tumor suppressor (LATS) kinases, which critically inhibit the YAP/TAZ transcription factors in transducing Hippo signaling. Our results suggest a model that APC/C<SUP>Cdh1</SUP> destabilizes LATS1/2 kinases in G1 phase of the cell cycle, leading to increased YAP/TAZ activities that promote G1/S transition by upregulating downstream gene expression, including <I>E2F1</I>. Our findings have important implications for a link between cell proliferation and LATS-regulated YAP/TAZ activities.</P><P>The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, large tumor suppressor (LATS) kinases and YAP/TAZ transcription factors, oscillate during mitotic cell cycle. We further identified that the anaphase-promoting complex/cyclosome (APC/C)<SUP>Cdh1</SUP> E3 ubiquitin ligase complex, which plays a key role governing eukaryotic cell cycle progression, intrinsically regulates Hippo signaling activities. CDH1 recognizes LATS kinases to promote their degradation and, hence, YAP/TAZ regulation by LATS phosphorylation is under cell cycle control. As a result, YAP/TAZ activities peak in G1 phase. Furthermore, we show in <I>Drosophila</I> eye and wing development that Cdh1 is required in vivo to regulate the LATS homolog Warts with a conserved mechanism. Cdh1 reduction increased Warts levels, which resulted in reduction of the eye and wing sizes in a Yorkie dependent manner. Therefore, LATS degradation by APC/C<SUP>Cdh1</SUP> represents a previously unappreciated and evolutionarily conserved layer of Hippo signaling regulation.</P>

유방암세포에서 LATS1/2 활성에 의한 당귀 추출물의 항암효과

김초롱,김남빈,정한솔,신유수,모정순 한의병리학회 2020 동의생리병리학회지 Vol.34 No.4

The Hippo-YAP signaling pathway is critical for cell proliferation, survival, and self-renewal in both Drosophila and mammals. Disorder of Hippo-YAP pathway leads to tumor development, progression and poor prognosis in various cancers. YAP/TAZ are the key downstream effectors of the Hippo pathway and they can be inhibited through LATS1/2, core kinases in the Hippo pathway, mediated phosphorylation. In this study, we investigated the effect of Angelica gigas Nakai extract (AGNE) on Hippo-YAP/TAZ pathway. First, ANGE induced YAP/TAZ phosphorylation and dissociation of the YAP/TAZ-TEAD transcription complex. By qRT-PCR, we found that ANGE inhibits the expression of YAP/TAZ-TEAD target gene, CTGF and CYR61. In addition, the transcriptional activity of YAP/TAZ was not suppressed significantly in LATS1/2 double-knockout (DKO) cells by ANGE compared to LATS1/2 wild-type (WT) cells, which means AGNE inhibits YAP/TAZ signaling through direct action on LATS1/2. Further, it was confirmed that AGNE-induced activation of LATS1/2 inhibited the migration potential of the vector-expressing cells by suppressing YAP/TAZ activity. The reduced migration potential was restored in active YAP-TEAD expressing cells. Taken together, the results of this study indicate that ANGE downregulates YAP/TAZ signaling in cells through the activation of LATS1/2.

Characteristics of _L -citrulline transport through blood-brain barrier in the brain capillary endothelial cell line (TR-BBB cells)

Lee, Kyeong-Eun,Kang, Young-Sook S. Karger Medical and Scientific Publishers 2017 JOURNAL OF BIOMEDICAL SCIENCE -BASEL- Vol.24 No.1

<P><B>Background</B></P><P><SUB>L</SUB>-Citrulline is a neutral amino acid and a major precursor of <SUB>L</SUB>-arginine in the nitric oxide (NO) cycle. Recently it has been reported that <SUB>L</SUB>-citrulline prevents neuronal cell death and protects cerebrovascular injury, therefore, <SUB>L</SUB>-citrulline may have a neuroprotective effect to improve cerebrovascular dysfunction. Therefore, we aimed to clarify the brain transport mechanism of <SUB>L</SUB>-citrulline through blood-brain barrier (BBB) using the conditionally immortalized rat brain capillary endothelial cell line (TR-BBB cells), as an in vitro model of the BBB.</P><P><B>Methods</B></P><P>The uptake study of [<SUP>14</SUP>C] L-citrulline, quantitative real-time polymerase chain reaction (PCR) analysis, and rLAT1, system b<SUP>0,+</SUP>, and CAT1 small interfering RNA study were performed in TR-BBB cells.</P><P><B>Results</B></P><P>The uptake of [<SUP>14</SUP>C] <SUB>L</SUB>-citrulline was a time-dependent, but ion-independent manner in TR-BBB cells. The transport process involved two saturable components with a Michaelis–Menten constant of 30.9 ± 1.0 μM (Km<SUB>1</SUB>) and 1.69 ± 0.43 mM (Km<SUB>2</SUB>). The uptake of [<SUP>14</SUP>C] <SUB>L</SUB>-citrulline in TR-BBB cells was significantly inhibited by neutral and cationic amino acids, but not by anionic amino acids. In addition, [<SUP>14</SUP>C]<SUB>L</SUB>-citrulline uptake in the cells was markedly inhibited by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), which is the inhibitor of the large neutral amino acid transporter 1 (LAT1), B<SUP>0</SUP>, B<SUP>0,+</SUP> and harmaline, the inhibitor of system b<SUP>0,+</SUP>. Gabapentin and <SUB>L</SUB>-dopa as the substrates of LAT1 competitively inhibited the uptake of [<SUP>14</SUP>C] <SUB>L</SUB>-citrulline. IC<SUB>50</SUB> values for <SUB>L</SUB>-dopa, gabapentin, <SUB>L</SUB>-phenylalanine and <SUB>L</SUB>-arginine were 501 μM, 223 μM, 68.9 μM and 33.4 mM, respectively. The expression of mRNA for LAT1 was predominantly increased 187-fold in comparison with that of system b<SUP>0,+</SUP> in TR-BBB cells. In the studies of LAT1, system b<SUP>0,+</SUP> and CAT1 knockdown via siRNA transfection into TR-BBB cells, the transcript level of LAT1 and [<SUP>14</SUP>C] <SUB>L</SUB>-citrulline uptake by LAT1 siRNA were significantly reduced compared with those by control siRNA in TR-BBB cells.</P><P><B>Conclusions</B></P><P>Our results suggest that transport of <SUB>L</SUB>-citrulline is mainly mediated by LAT1 in TR-BBB cells. Delivery strategy for LAT1-mediated transport and supply of L-citrulline to the brain may serve as therapeutic approaches to improve its neuroprotective effect in patients with cerebrovascular disease.</P>

Expression of Amino Acid Transporter LAT1 During Ameloblast Differentiation

Sang-Bong Kim,Do-Kyung Kim,Chun-Sung Kim,Joong-Ki Kook,Joo-Cheol Park,Heung-Joong Kim KOREAN ACADAMY OF ORAL BIOLOGY 2009 International Journal of Oral Biology Vol.34 No.3

Amino acid transporters play important roles in supplying nutrients to cells. In our current study, we investigated the expression of LAT1 and measured the amino acid uptake in ameloblast cultures to further elucidate the roles of this transporter during the differentiation of these cells. RT-PCR, observations of cell morphology, Alizaline red-S staining, and uptake analyses were performed following the experimental induction of differentiation in the cultures. LAT1 mRNA was detectable and found to gradually increase over time whereas LAT2 mRNA was not evident in the ameloblast cultures. Transcripts of 4F2hc, a cofactor of LAT1 and LAT2, were also found to be expressed in ameloblast cultures and increase with time. Amelogenin mRNA was expressed in the early stage ameloblast cultures. L-leucine uptake was observed to increase over 14 days of growth in culture. Our data suggest that LAT1 has a key role in the differentiation of ameloblasts and in providing these cells with neutral amino acids, including several essential amino acids.