高国全
病理性血管增生的生化改变和分子机制;血管增生抑制因子的膜受体、信号传导通路及基因表达调控;血管增生抑制因子治疗血管增生性疾病(如肿瘤和糖尿病血管并发症)的基础研究和临床试验。
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- 姓名:高国全
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学术头衔:
博士生导师
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学科领域:
生物化学
- 研究兴趣:病理性血管增生的生化改变和分子机制;血管增生抑制因子的膜受体、信号传导通路及基因表达调控;血管增生抑制因子治疗血管增生性疾病(如肿瘤和糖尿病血管并发症)的基础研究和临床试验。
高国全,男,一九六五年七月出生,现任中山大学基础医学院生物化学教研室主任,广东省生物化学学会常务理事、秘书长。1997年6月 在中山医科大学获得医学博士学位(生物化学专业);1999年晋升副教授;2004年晋升教授并获中山大学教师特别津贴,入选广东省高等学校“千百十工程”校级培养对象。1999.1-2002.5期间,在美国进行博士后研究工作并于2002年一月份晋升为研究助理教授(Research Assistant Professor ),方向是糖尿病血管病变的机制和治疗;取得了一系列重要成果并发表在国际著名的科学杂志上,如Diabetes (影响因子9.1), Journal of Biological Chemistry (影响因子7.3) 等;到目前为止,已有9篇文章正式发表(第一作者发表文章5篇)。2002年回国后,获得学校985学科建设基金100万元,组建了先进的分子生物学实验室,建立了一支结构合理、有良好的技术背景和实验基础的科研队伍。在以往国外的工作基础上结合我国血管增生性疾病的需要,确定研究方向为:病理性血管增生的生化改变和分子机制;血管增生抑制因子的膜受体、信号传导通路及基因表达调控;血管增生抑制因子治疗血管增生性疾病(如肿瘤和糖尿病血管并发症)的基础研究和临床试验。截止目前已获得国家自然科学基金、CMB学者项目、广州市科技攻关重点项目、教育部回国人员启动基金等多项基金超过100万元的资助,研究工作进展顺利,已发表相关文章8篇,申请发明专利一项。
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高国全, 蔡卫斌, 刘倩平
,-0001,():
-1年11月30日
纤溶酶原Kringle 5是纤溶酶原中与血管抑素相连的另一个联环结构域,它能抑制内皮细胞的增殖、迁移,并能诱导内皮细胞凋亡和细胞周期停滞,具有很强的抑制血管生成活性,是抑制活性最强的纤溶酶原水解片段。同时它具有分子量小、性质稳定、毒副作用小、特异性高等优点,是一个有潜在临床应用价值和开发前景的治疗血管增生性疾病的药物。
纤溶酶原, Kringle 5, 血管增生, 内皮细胞
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【期刊论文】人纤溶酶原K5突变体I的构建及其在大肠杆菌中的表达与纯化
高国全, 蔡卫斌, 李朝阳, 杨中汉, 骆晓枫, 周世豪, 李民友, 刘祖国
中山大学学报(医学科学版)(2004)25:121-124,-0001,():
-1年11月30日
【目的】构建人纤溶酶原Kringle 5(K5)的突变Cys461-Cys540(K5 mutl)在大肠杆菌中表达,亲和层析纯化,为探讨K5抗血管增生活性与Kringle结构域的关系提供基础。【方法】以K5全长cDNA为模板用PCR的方法扩增人纤溶酶原K5 mutl基因,将其克隆进表达载体Pet-22b(+)中,并用限制性核酸内切酶酶切和DNA测序鉴定其连接正确pET-22b(+)/K5 mutl转化大肠杆菌BL21(DE3),IPTC诱导表达:表达产物用固化Ni2*-His Bind Resin亲和层析方法纯化,用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)和Westernblot方法分析鉴定。【结果】PCR扩增获得258bp的人纤溶酶原K5 mutl基因片段,正确插入Pet-22b(+)载体,在大肠杆菌中该基因编码蛋白的表达量占菌体总蛋白13%左右SDP-PACE显示其相对分子质量M≈14.1×103,Western blot证实该表达蛋白为K5 mutl重组蛋白,经亲和层析后K5 mutl重组蛋白纯度大于90%,获得率约为10mg/L。【结论】成功构建人纤溶酶原K5 mutl,实现在大肠杆菌中高效表达:亲和层析纯化获得较高纯度K5 mutl重组蛋白
纤溶酶原, 突变型K5, 血管增生抑制因子, 突变, 基因表达
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高国全, 马建芳, 杨中, 宋志宏, 郭颖, 蔡卫斌, 刘倩平, 郭琳琅
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-1年11月30日
目的 检验大剂量葡萄糖水平对培养的原代人视网膜毛细血管内皮细胞(human retinal capillary endothelial cells,HRCEC)的直接影响!方法 HRCEC细胞从捐赠人眼中分离得到。细胞在含有5mmol/L或5mmol/L葡萄糖的培养基中培养6d。应用锥虫蓝染色测定细胞活力流式细胞计数分析细胞周期、RUNWL分析细胞凋亡。结果 HRCEC细胞在25mmol/L葡萄糖中培养6d,细胞活力显著下降。通过流式细胞计数和TUNEL测定凋亡细胞的数目在大剂量葡萄糖培养基中显著升高!结论 大剂量葡萄糖可诱导人视网膜毛细血管内皮细胞凋亡,这有可能是促进糖尿病性视网膜病发展的原因!
视网膜病,, 糖尿病性, 凋亡#, 视网膜内皮细胞, 高血糖症, 流式细胞计数
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高国全, S. X. Zhang, J. Sima, C. Shao, J. Fant, Y. Chen, B. Rohrer, G. Gao, J-x. Ma
Diabetologia (2004)47:124-131,-0001,():
-1年11月30日
Aims/hypothesis. Retinal vascular leakage is an early pathological feature in iabetic retinopathy and can lead to macular oedema and loss of vision. Previouslywe ave shown that plasminogen kringle 5 (K5), an angiogenic inhibitor, inhibits retinal eovascularisation in the rat model of oxygen-induced retinopathy (OIR). The purpose f this study was to examine the effect of K5 on vascular leakage in the tina. Methods. Neonatal rats were exposed to hyperoxia to induce OIR. Diabetes was induced in adult rats by injecting streptozotocin. Vascular permeability was measured by Evans blue method. Expression of vascular endothelial growth factor (VEGF) was evaluated using immunohistochemistry and western blot analysis. Results. Rats with OIR and diabetes showed abnormal vascular hyperpermeability in the retina and iris. Intravitreal injection of K5, reduced vascular permeability in both animal models, but did not affect permeability in normal rats. K5 reduced vascular ermeability at doses substantially lower than that required for inhibition of retinal neovascularisation. The K5-induced reduction in vascular permeability correlated with its down-regulation of VEGF expression in the retina. Moreover, K5 inhibited IGF-1-induced yperpermeability, which is known to arise through up-regulation of endogenous VEGF expression. However, K5 had no effect on the hyperpermeability induced by injectionof exogenous VEGF. onclusions/interpretation. Very low doses of K5 reduce pathological vascular leakage in the retina. K5 thus has therapeutic potential in the treatment of diabetic macular oedema. This effect can be ascribed, at least in part, to the down-regulation of endogenous VEGF expression.
Diabetic retinopathy
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高国全, Guoquan Gao, Yan Li, Stephen Gee, Andrew Dudley, James Fant, Craig Crosson, and Jian-xing Ma‡
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-1年11月30日
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高国全, D. Zhang, P. L. Kaufman, G. Gao R. A. Saunders, J. X. Ma
Diabetologia (2001)44:757-756,-0001,():
-1年11月30日
Aims/hypothesis. Plasminogen kringle 5 is an endoge-nous angiogenic inhibitor. The purpose of the resent study was to explore the potential application of kringle 5 in the treatment of retinal eovascularization. Methods. Plasminogen kringle 5 was expressed in E. coli and affinity-purified. Its nti-angiogenic activity was determined in cultured primary human capillary endothelial cells. Retinal eovascularization was in-duced in newborn rats by exposure to hyperoxia and then normoxia. Kringle 5 as intravitreally injected into the rat model. Retinal neovascularization was vi-sualized by luorescein angiography on flat-mounted retina and quantified by counting preretinal vascular cells. Results. Plasminogen kringle 5 inhibited primary endothelial cells but not retinal neuronal ells, suggesting cell type-specific inhibition. The oxygen-induced retinopathy rat model showed an ver-expression of vascular endothelial growth factor, preretinal neovas-cularization and haemorrhage. ntravitreal injection of kringle 5 before the development of neovascular-ization resulted in fewer eovascular tufts and pre-retinal vascular cells than in control rats with PBS injection (p<0.01). oreover, injection of krin-gle 5 after the development of neovascularization in-hibited the increase n the preretinal vascular cells (p<0.05). These results suggest that kringle 5 both prevents the evelopment and arrests the progression of retinal neovascularization. The injection of kringle 5 did ot result in any detectable inflammatory re-sponse in the retina or histological toxicity to retinaneurons and pre-existing vessels. Conclusion/interpretation. These observations sug-gest that ntravitreal delivery of angiogenic inhibitors could have therapeutic benefits in neovascular dis-eases of the retina.
Angiogenesis,, angiogenic inhibitor,, an-giostatin,, diabetes,, retinopathy of prematurity.,
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高国全, Sardar Y.K. Yousufzai, Guoquan Gao, Ata A. Abdel-Latif*
European Journal of Pharmacology 407, 2000, 17-26,-0001,():
-1年11月30日
The purpose of this study was to investigate the potential role of mitogen-activated protein (MAP) kinase in contraction by monitoring MAP kinase phosphorylation (activation) and contraction during agonist stimulation of cat iris phincter smooth muscle. Changes in tension in response to rostaglandin F2a, latanoprost, a prostaglandin F2a analog used as an anti-glaucoma drug, and carbachol were recorded isometrically, and MAP kinase activation was monitored by Western blot using a phosphospecific p42/P44 MAP kinase antibody. We found that treatment of the muscle with 2'Amino-3'methoxyflavone (PD98059) (10umM), a specific inhibitor of MAP kinase kinase (MEK), inhibited ignificantly prostaglandin F2a-and latanoprost-induced phosphorylation and contraction, but had little 2a effect on those voked by carbachol. Prostaglandin F2a increased MAP kinase phosphorylation in a concentration-dependent manner with EC50 value of 1.1
Nonvascular smooth muscle, Mitogen-activated protein kinase, Contraction, Prostaglandin F2a, Carbachol
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【期刊论文】Unbalanced expression of VEGF and PEDF in schemia-induced retinalneovascularization
高国全, Guoquan Gao, Yan Li, Dongchang Zhang, Stephen Gee, Craig Crosson, Jian-xing Ma*
FEBS Letters 489(2001)270-276,-0001,():
-1年11月30日
Abstract Retinal levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived actor (PEDF), an angiogenic inhibitor, were measured and correlated with the ischemia-induced retinal eovascularization in rats. The retinas with neovascularization showed a 5-fold increase in VEGF while2-fold decrease in PEDF, compared to the age-matched controls, resulting in an increased EGF/PEDF ratio. The time course of the VEGF/PEDF ratio change correlated with the progression ofretinal neovascularization. Changes in the VEGF and PEDF mRNAs preceded their protein level anges. hese results suggest that an unbalance between angiogenic stimulators and inhibitors may contribute to retinal neovascularization. fl 2001 Federation of European Biochemical Societies. Published byElsevier Science B.V. All rights reserved.
Angiogenesis, Angiogenic inhibitor, Diabeticretinopathy, Growth factor, Pigment pithelium-derivedfactor, Retinal ovascularization
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【期刊论文】Tipping the balance forangiogenic disorders
高国全, Guoquan Gao, and Jianxing Ma
DDT Vol. 7, No. 3 February 2002,-0001,():
-1年11月30日
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