운동이 F344계 임신쥐에서 골격근의 VAMP-2 및 GLUT-4 단백질 발현과 혈중 인슐린, 렙틴 농도에 미치는 영향

윤진환,이희혁,김종오,오명진,박성태,지용석,서태범,남궁욱,Yoon, Jin-Hwan,Lee, Hee-Hyuk,Kim, Jong-Oh,Oh, Myung-Jin,Park, Seong-Tae,Jee, Young-Seok,Seo, Tae-Beom,NamGung, Uk 한국생명과학회 2007 생명과학회지 Vol.17 No.6

본 연구는 임신횐쥐에서 운동이 혈중 인슐린과 렙틴 농도, 그리고 골격근의 GLUT-4와 VAMP-2단백질 발현에 변화를 조사하기 위하여 수행되었다. 본 연구에서 비임신 횐쥐에 비해 임신 횐쥐에서 혈중 인슐린 농도가 유의하게 증가되었고, 렙틴 농도는 유의하게 감소하는 것으로 나타났다. 임신횐쥐에게 달리기 운동을 적용한 결과 임신으로 증가된 인슐린 농도를 유의하게 감소시키면서 렙틴 농도의 감소를 억제시키는 것으로 나타났다. 골격근에서 GLUT-4와 VAMP-2 단백질 발현량을 조사한 결과 비임신 횐쥐에 비해 임신 횐쥐에서 이러한 단백질 발현이 유의하게 감소되었지만, 임신 중 달리기운동을 경험한 횐쥐에서 GLUT-4와 VAMP-2 발현 모두 유의하게 증가되는 것으로 나타났다. 이와 잘이 임신으로 인한 혈중 인슐린 및 렙틴의 변화가 골격근에서 당을 근조직으로 흡수하는 신호 전달 경로와 수송체의 발현 손상과 연관되어있음을 보여주는 것이다. 하지만 임신 횐쥐에서 달리기 운동은 인슐린과 렙틴 농도의 변화를 완화시킴으로써 골격근의GLUT-4와 VAMP-2발현을 유의하게 증가시키는 것으로 나타났다. The main objective of this study was to investigate the effects of exercise on serum insulin and leptin levels and GLUT-4 and VAMP-2 in skeletal muscles from the pregnant rats. F344 rats were randomly divided into four groups (n = 15 in each group): control group (CG), pregnant group (PG), pregnant running group (PR), and pregnant swimming group (PS). From the 15th day of pregnancy, animals in the running group were forced to run on treadmill for 30 min with a light intensity, while those in the swimming group were forced to swim in swimming pool for 10 min once a day for 6 consecutive days. The present result demonstrated that in pregnant rat group, serum insulin levels significantly in-creased and leptin levels significantly decreased. Skeletal GLUT-4 and VAMP-2 protein expression was significantly decreased in pregnant rats compared to non-pregnant rats. However, matenal running during gestational period alleviated pregnancy-induced changes in plasma insulin and leptin levels, and it significantly enhanced skeletal GLUT-4 and VAMP-2 protein expression. From those results, it can be suggested that running exercise during gestational period may improve glycemic control by up-regulating GLUT-4 and VAMP-2 protein expression.

Significance of Vesicle-Associated Membrane Protein 8 Expression in Predicting Survival in Breast Cancer

Mengci Yuan,Jianhua Liao,Ji Luo,Mengyao Cui,Feng Jin 한국유방암학회 2018 Journal of breast cancer Vol.21 No.4

Purpose: Vesicle-associated membrane protein 8 (VAMP8) is a soluble N-ethylmaleimide-sensitive factor receptor protein that participates in autophagy by directly regulating autophagosome membrane fusion and has been reported to be involved in tumor progression. Nevertheless, the expression and prognostic value of VAMP8 in breast cancer (BC) remain unknown. This study aimed to evaluate the clinical significance and biological function of VAMP8 in BC. Methods: A total of 112 BC samples and 30 normal mammary gland samples were collected. The expression of VAMP8 was assessed in both BC tissues and normal mammary gland tissues via a two-step immunohistochemical detection method. Results: The expression of VAMP8 in BC tissues was significantly higher than that in normal breast tissues. Furthermore, increased VAMP8 expression was significantly correlated with tumor size (p=0.007), lymph node metastasis (p= 0.024) and recurrence (p=0.001). Patients with high VAMP8 expression had significantly lower cumulative recurrence-free survival and overall survival (p<0.001 for both) than patients with low VAMP8 expression. In multivariate logistic regression and Cox regression analyses, lymph node metastasis and VAMP8 expression were independent prognostic factors for BC. Conclusion: VAMP8 is significantly upregulated in human BC tissues and can thus be a practical and potentially effective surrogate marker for survival in BC patients.

Synaptotagmin 5 Controls SYP132-VAMP721/722 Interaction for Arabidopsis Immunity to Pseudomonas syringae pv tomato DC3000

Kim, Soohong,Kim, Hyeran,Park, Keunchun,Cho, Da Jeong,Kim, Mi Kyung,Kwon, Chian,Yun, Hye Sup Korean Society for Molecular and Cellular Biology 2021 Molecules and cells Vol.44 No.9

Vesicle-associated membrane proteins 721 and 722 (VAMP721/722) are secretory vesicle-localized arginine-conserved soluble N-ethylmaleimide-sensitive factor attachment protein receptors (R-SNAREs) to drive exocytosis in plants. They are involved in diverse physiological processes in plants by interacting with distinct plasma membrane (PM) syntaxins. Here, we show that synaptotagmin 5 (SYT5) is involved in plant defense against Pseudomonas syringae pv tomato (Pst) DC3000 by regulating SYP132-VAMP721/722 interactions. Calcium-dependent stimulation of in vitro SYP132-VAMP722 interaction by SYT5 and reduced in vivo SYP132-VAMP721/722 interaction in syt5 plants suggest that SYT5 regulates the interaction between SYP132 and VAMP721/722. We interestingly found that disease resistance to Pst DC3000 bacterium but not to Erysiphe pisi fungus is compromised in syt5 plants. Since SYP132 plays an immune function to bacteria, elevated growth of surface-inoculated Pst DC3000 in VAMP721/722-deficient plants suggests that SYT5 contributes to plant immunity to Pst DC3000 by promoting the SYP132-VAMP721/722 immune secretory pathway.

Vesicle-associated membrane proteins 721 and 722 are required for unimpeded growth of Arabidopsis under ABA application

Yi, C.,Park, S.,Yun, H.S.,Kwon, C. G. Fischer 2013 Journal of plant physiology Vol.170 No.5

Soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins are core factors in driving vesicle fusion with target membranes, which is critical in eukaryotes having distinct subcellular organelles. Amongst them, vesicle-associated membrane proteins (VAMP) 721 and 722 are involved in plant growth/development and immunity. In the course of stress responses, plants often show retarded growth. The precise mechanism of this retardation is not fully understood. The plant stress hormone abscisic acid (ABA), which can cause growth inhibition, down-regulates VAMP721/722 protein levels but not transcript levels. Enhanced growth inhibition and early depletion of the amount of VAMP721/722 caused by ABA in haploinsufficient VAMP721<SUP>+/-</SUP>VAMP722<SUP>-/-</SUP> and VAMP721<SUP>-/-</SUP>VAMP722<SUP>+/-</SUP> plants suggest that ABA impedes plant growth in part by reducing VAMP721/722 proteins. Since VAMP721/722 are engaged in exocytosis, our data implies that ABA-induced growth retardation may result from diminished secretory activities leading to decreased transport of molecules required for plant growth in the plasma membrane and cell wall.

Requirement of Vesicle-Associated Membrane Protein 721 and 722 for Sustained Growth during Immune Responses in Arabidopsis

윤혜섭,권지안,Mark Kwaaitaal,Naohiro Kato,이창현,박소현,Masa H. Sato,Paul Schulze-Lefert 한국분자세포생물학회 2013 Molecules and cells Vol.35 No.6

Extracellular immune responses to ascomycete and oomycete pathogens in Arabidopsis are dependent on vesicle-associated secretion mediated by the SNARE proteins PEN1 syntaxin, SNAP33 and endomembrane-resi-dent VAMP721/722. Continuous movement of func-tional GFP-VAMP722 to and from the plasma membrane in non-stimulated cells reflects the second proposed function of VAMP721/722 in constitutive secretion during plant growth and development. Application of the bacterium-derived elicitor flg22 stabilizes VAMP721/722 that are otherwise constitutively degraded via the 26S proteasome pathway. Depletion of VAMP721/722 levels by reducing VAMP721/ 722 gene dosage enhances flg22-induced seedling growth inhibition in spite of elevated VAMP721/722 abundance. We therefore propose that plants prioritize the deployment of the corresponding secretory pathway for defense over plant growth. Interstingly, VAMP721/722 specifically interact in vitro and in vivo with the plasma membrane syntaxin SYP132 that is required for plant growth and resistance to bacteria. This suggests that the plant growth/immunity-involved VAMP721/722 form SNARE complexes with multiple plasma membrane syntaxins to discharge cue-dependent cargo molecules.

카테킨 섭취와 운동수행에 따른 obese Zucker rat 골격근의 GLUT-4 VAMP-2와 Syntaxin-4 단백질 발현의 변화

김철현,임예현,조인호,김성찬,방상식,조준용,이규성 한국운동과학회 2003 운동과학 Vol.12 No.4

김철현, 임예현, 조인호, 김성찬, 방상식, 조준용, 이규성, 카테킨 섭취와 운동수행에 따른 obese Zucker rat 골격근의 GLUT-4, VAMP-2와 Syntaxin-4 단백질 발현의 변화. 운동과학, 제12권 제4호, 663-678, 2003. 골격근에서 인슐린의 자극은 GLUT4를 세포막으로 전좌하도록 활성화하여 세포내로 글루코스를 공급할 수 있도록 한다. GLUT4의 전좌는 특이적인 액포(vesicle)결합 단백질인 v-SNARE가 표적 세포막에 위치한 상동성이 큰 t-SNAHE(Syntaxin-4)단백질을 특이적으로 인식하고 상호작용하여 GLUT-4를 세포막 표면으로 가역적 전좌(translocation)를 시켜 글루코스 섭취 능력을 증가시킨다. 본 연구는 v-와 t-SNARE 단백질의 상호 신호전달 작용 및 GLUT-4 작용 기전을 규명하고, 운동과 녹차 성분인 카테킨 섭취에 따른 골격근의 인슐린 저항성에 미치는 영향을 구명하는데 그 목적이 있다. 이를 위해, 본 연구는 비만동물로 확립된 obese Zucker rat(fa/fa)를 사용하여 실험을 수행하였다. 집단은 비교집단, 카테킨 섭취, 운동집단, 운동과 카테킨 섭취 집단(4집단)으로 구분하여 8주간 실험을 실시하였다. 실험결과 카테킨 섭취는 운동수행은 독립적으로 obese Zucker rat의 골격근내 인슐린 조절 단백질인 GLUT-4와 Vamp-2, Syntaxin-4 단백질 발현을 증가시킨 것으로 나타났다. 이는 운동 혹은 카테킨은 각각 독립적으로 골격근의 글루코스 섭취 능력 및 인슐린 저항성을 개선시키는데 도움이 되는 것을 확인할 수 있었다. 즉, 운동 영양학 측면에서 카테킨과 같은 항당뇨 관련 보조물 섭취는 운동과 함께 비만과 당뇨병 개선 효과를 극대화시키는데 도움이 될 것으로 나타났다. 그러나 운동에 의한 GLUT-4의 세포막 이동 외에 카테킨 섭취가 GLUT-4의 세포막으로 이동에 있어서 또 다른 기전에 관여할 가능성이 있어 카테킨 섭취에 따른 GLUT-4 이동의 기전을 다시 확인하기 위한 후속 연구가 필요하다. Kim, C.H., Leem, Y.H., Cho, I.H., Kim, S.C., Bang, S.S., Cho, J.Y.,Lee, K.S. The effect of exercise training and catechins supplementation on skeletal muscle GLUT-4, VAMP-2 and Syntaxin-4 protein expression in obese Zucker rats. Exercise Science, 12(4): 653-670, 2003. Studies have suggested an important role for synaptobrevin and syntaxin homologues in this event, particularly the v-soluble N-ethylmaleimide attachment protein receptors(SNAREs)cellubrevin and vesicle-associated memo r ane protein-2(VAMP-2) and the syntaxin-4(t-SNARE) but the expression of these proteins has not been studied in insulin resistant tissues. There fore, we examined SNARE protein content in skeletal muscle from obese Zucker rats and determined the effect of exorcise and/or catechin treatment on these proteins. GLUT4 levels in skeletal muscle from exorcise and/or catechin treatments were elevated compared with control group. VAMP-2, and syntaxin 4 protein levels were elevated in skeletal muscle from obese Zuker rats compared with controls Restoration of normo-glycemia and normo-insulinemia in exorcised obese Zuker rats improved VAMP-2, and syntaxin-4 protein to levels approaching normal in lean animals. These data show that elevated v- and t-SNARE protein levels are associated with insulin resistance in skeletal muscle and that these increase may be achieved by exorcise and/or catechin treatments concomitant with a restoration of glycemic control. in summary, we have demonstratedthat v- and 1- SNAHE concentration as well as muscle GLUT-4 protein and mRNA can increase significantly after prolonged exorcise and/or catechin, and confirmed that this increase in GLUT-4 protein is controlled at both the pre-translational and translational levels. The observation that improved glucose storage suggests that the increased expression of GLUT-4 protein expression can serve as a molecular yardstick for exorcise-dependent glycogen deposition.

α-Synuclein Disrupts Vesicle Fusion by Two Mutant-Specific Mechanisms

Gyeongji Yoo,Hyeong Jeon An,Sanghun Yeou,Nam-Ki Lee 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.11

Synaptic accumulation of α-synuclein (α-Syn) oligomers and their interactions with VAMP2 have been reported to be the basis of synaptic dysfunction in Parkinson’s disease (PD). α-Syn mutants associated with familial PD have also been known to be capable of interacting with VAMP2, but the exact mechanisms resulting from those interactions to eventual synaptic dysfunction are still unclear. Here, we investigate the effect of α-Syn mutant oligomers comprising A30P, E46K, and A53T on VAMP2-embedded vesicles. Specifically, A30P and A53T oligomers cluster vesicles in the presence of VAMP2, which is a shared mechanism with wild type α-Syn oligomers induced by dopamine. On the other hand, E46K oligomers reduce the membrane mobility of the planar bilayers, as revealed by single-particle tracking, and permeabilize the membranes in the presence of VAMP2. In the absence of VAMP2 interactions, E46K oligomers enlarge vesicles by fusing with one another. Our results clearly demonstrate that α-Syn mutant oligomers have aberrant effects on VAMP2-embedded vesicles and the disruption types are distinct depending on the mutant types. This work may provide one of the possible clues to explain the α-Syn mutant-type dependent pathological heterogeneity of familial PD.

The microRNA-127-3p directly targeting Vamp2 in C2C12 myoblasts

Jie Li,Gaofu Wang,Jing Jiang,Lin Fu,Peng Zhou,Hangxing Ren 한국통합생물학회 2018 Animal cells and systems Vol.22 No.5

MicroRNAs (miRNAs) have been reported that can regulate skeletal muscle growth and development. Previously, we demonstrated that miR-127-3p were differently expressed in skeletal muscle and muscle cells. However, the molecular mechanism of miR-127-3p regulation of skeletal myogenesis are not well elucidated. In this study, we transfected miR-127-3p into C2C12 cells, and found miR-127-3p induces myogenesis by targeting Vamp2. Moreover, the regulatory mechanism of Vamp2 in myoblasts proliferation and differentiation was further confirmed. In conclusion, our data providedevidences that miR-127-3p reciprocally regulated myoblasts proliferation and differentiation through directly targeting Vamp2.

Association of VAMP-2 and Syntaxin 1A Genes with Adult Attention Deficit Hyperactivity Disorder

Ay˚e Nur Inci Kenar,Özlem I˙zci Ay,Hasan Herken,Mehmet Emin Erdal 대한신경정신의학회 2014 PSYCHIATRY INVESTIGATION Vol.11 No.1

Objective The etiology of attention deficit hyperactivity disorder (ADHD) has not been entirely clarified yet. Structural and metabolicdifferences at the prefrontal striatal cerebellary system and the interaction of gene and environment are the main factors that thought toplay roles in the etiology. Genetic investigations are performed especially about the dopamine pathways and receptors. In this study; itwas aimed to investigate the association of the synaptobrevin-2 (VAMP-2) gene Ins/Del polymorphism and syntaxin 1A gene intron7 polymorphism, which take place in encoding presynaptic protein, with adult ADHD. Methods One hundred thirty-nine patients, having ADHD aging between 18 and 60 years and 106 healthy people as controls were includedinto the study. DNA samples were extracted from whole blood and genetic analysis were performed. ResultsaaA significant difference was determined between ADHD and VAMP-2 Ins/Del polymorphism and syntaxin 1A intron 7 polymorphismaccording to the control group. These polymorphisms were found not to be associated with subtypes of ADHD. Conclusion It is supposed that synaptic protein genes together with dopaminergic genes might have roles in the etiology of ADHD.

장기간 운동이 골격근의 GLUT-4 전좌에 미치는 영향

노정호(Jung Ho Noh),윤경호(Kyoung Ho Yoon),박수연(Soo Yeon Park) 한국사회체육학회 2012 한국사회체육학회지 Vol.0 No.47

The purpose of this study in to investigate plasma membrane and/or intracellular Vamp2, Syntaxin4, GLUT-4 protein and total muscle glycogen concentration in skeletal muscle following long-tern exercise. Subjects who were underwent ACLR were divided into two groups (training group, n=5 and control group, n=5). Syntaxin4 protein expression is markedly increased in TRAINING compared to CON. GLUT-4 and Vamp2 in plasma membrane were significantly overexpressed in TRAINING (p<.05; .001); But, GLUT-4 and Vamp2 protein in an intracellular portion were significantly lower in TRAINING compared to CON (p<.05; .001). Total glycogen concentration was significantly higher in TRAINING compared to CON (p<.001). In these results, Increased glycogen content of skeletal muscle with exercise training adaptation is likely due to interactions of higher membrane GLUT-4 protein expression with v-t SNARE complex.