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专访AMPK之父Grahame Hardie教授:代谢关键分子与癌症

专访AMPK之父Grahame Hardie教授:代谢关键分子与癌症



2016年9月19-23日由冷泉港亚洲举办的Cancerand Metabolism学术会议在苏州举行。有“AMPK之父”之称的英国邓迪大学教授Grahame Hardie作为特邀嘉宾做了主题演讲:“AMP-Activated Protein Kinase – Tumour Suppressor Or Oncoprotein?”。生物探索非常有幸在会后对他进行了采访。
1AMPK是什么AMPK 即AMP依赖的蛋白激酶,是生物能量代谢调节的关键分子。所有细胞里能量消耗的反应都是由高比值的ATP/ADP所驱动,当能量压力让这个比例降低时,AMPK系统就启动了。激活AMPK,一方面关闭消耗ATP的合成代谢途径,另一方面启动产生ATP的分解代谢途径。当细胞能量储备低时可改变细胞致力生成更多的ATP。故一直以来被认为是细胞内最重要的“细胞能量调节器”。Hardie教授的实验室是最先发现AMPK级联通路的,多年来一直围绕这个激酶做了大量重要的工作。
近年来,随着AMPK研究的深入,发现其下游靶蛋白数量众多,具有多种重要的生物学效应。AMP激酶信号通路已被证实与癌症、糖尿病、食欲控制和昼夜节律等有关。
Hardie教授介绍说他们发现AMPK级联通路还是在上世纪七十年代,在研究代谢途径的过程中他们分离了该激酶,开发了新的方法来分析它。现在它已经变成了参与各种代谢途径的关键,他说他那时也没有想到如今AMPK是这样地重要。
2AMPK在癌症中的作用由于AMPK在抑制癌细胞生长和增殖中的作用,已作为一种很有前途的化疗药物潜在靶标。但2012年Nature发表的一篇文章发现当细胞处于代谢压力下,AMPK的激活会促进细胞的存活,防止细胞死亡。
我们就此问询了Hardie教授如何理解AMPK在癌症中的作用。Hardie教授说传统的来说大家认为AMPK是抑制癌症的,但是最近的证据表明并不总是这样。到底是抑制者还是促进者,很难从这两个对立面得出结论。他介绍说他昨天在冷泉港亚洲会议上做的主题报告就提出在某些条件下它是癌症的抑制者,另一些条件下是促进者。提出的这种观点确实是一个相当新的概念。
当癌细胞起初离开肿瘤细胞外基质到迁移、传播过程中,肿瘤细胞受到代谢压力。当葡萄糖摄取减少时,激活的AMPK实际上是癌细胞代谢应激期间生存必须的。AMPK通过间接调节NADPH促进癌细胞的生存,在这种状况下可以认为AMPK是癌症的促进者。
既然AMPK是即是癌症的抑制者又是促进者,这种双重作用是不是让大家想以AMPK为药靶治疗癌症的想法变得很困难呢?Hardie教授做出解释说AMPK参与的作用非常广泛,也许我们能设计AMPK的抑制剂希望其治疗癌症,但是它可能会带来不少其它的副作用。不是说不可能将AMPK作为药靶,但是会比较困难。
3AMPK与阿司匹林Hardie教授的团队在2012年Science杂志发布的一篇文章中证实水杨酸直接激活了AMP激酶,通过调控细胞的ATP水平,促进了小鼠体内的脂肪燃烧。水杨酸是阿司匹林的一种成分,Hardie教授说当你服用阿司匹林它就降解成水杨酸。这项研究阐明了阿司匹林可直接激活与肿瘤抑制和血糖调控相关的一条信号通路,这或许可以解释阿司匹林的某些长期健康益处,例如在预防癌症方面的作用。
鉴于AMP激酶在细胞代谢中的关键作用,水杨酸对于AMP激酶的所有效应均具有一定的影响。Hardie教授说他们还没有完全回答清楚这个问题。
阿司匹林并非是万能药。任何人都不应该寄希望阿司匹林能够同时降低血糖、燃烧脂肪和预防癌症。这条信号通路的发现或可促使科学家们未来开发出更安全更有效的药物。
4关于科研的感想Hardie教授提出虽然人们通常认为设计、艺术的工作是创造性的,但科学家的工作也是极富创造力的。你提出了一个想法,为了证实它,你还需要其它许多技能,比如说逻辑。要做好一个科学家的工作很重要的一点是坚持,因为研究工作并不容易,耗费大量的时间,你得持之以恒。而且很多时候,政府希望能够很快从研究项目中获益,但实际上需要很多年的工作。不仅仅是科学家,资助科学的人也要习惯长期而不是短期能有收益。
Hardie教授对冷泉港亚洲会议的印象很好,觉得环境很宜人。现在中国对世界有着巨大的影响力,中国科研对全球科研界的影响也日益显著,所以访问中国也是很重要的。他向我们介绍他已经是两个中国大学的访问教授。
冷泉港亚洲
冷泉港亚洲沿袭美国冷泉港实验室的传统,为来自亚洲乃至全球的科学家及学生们,提供近距离分享最新科研进展的独特平台。在冷泉港亚洲,与会者不论地位、年龄、国籍、性别、种族,都将于会议全程得到平等自由的交流机会。冷泉港亚洲会议的最大特色,就是大部分在会议上发表的演讲,选择自全体与会者公开提交的摘要中(年会除外),报告涵盖了大量未发表的最新科研进展。
通常,冷泉港亚洲会为每次会议指定一个小型国际组委会(3-5名来自不同国家或地区的卓越学者),来负责会议的组织和安排。该组委会在议题设立、各分会(session)设定及报告人和海报(Poster)筛选等相关范畴,享有完全的学术自主权。与会者在冷泉港亚洲官方网站www.csh-asia.org提交注册信息后,会立即收到包含有摘要提交链接的确认邮件。所有在线提交的摘要,将于截止日期后一周内寄送给会议组委会,由他们根据摘要质量及与会议议题契合度,筛选出进行口头演讲及海报展示的优秀作品。被选定摘要及状态会在会议开始前3-4周于官网公布。组委会将根据选出的摘要,设定会议讨论议程及分议题,与会者在抵达会场后方可由摘要集获知会议详细日程及每一报告的具体安排。
冷泉港亚洲会议一般历时3-5天,由高密度的演讲分会、海报展示分会及各类社交活动组成。每一位演讲者的报告时间约为15-20分钟,台下听众将有5分钟的时间与演讲者进行交流问答。海报展示分会一般安排在下午,每一位作者都将有机会,就自己的研究成果及感兴趣的话题,与来自世界各地的学者们进行充分探讨。除常规的演讲与海报展示分会外,
冷泉港亚洲还将组织一系列鸡尾酒会、晚宴、舞会,或音乐会。轻松自如的氛围,消除了一切来自背景的隔阂,与会者之间的距离被无限拉近,灵感与火花不断涌现及碰撞着。冷泉港亚洲会议不止于演讲形式的各种互动,将使每一位与会者收益颇丰。信息传递不再是传统的单向,独特的会议模式使得科学探讨的沟通渠道多元而畅通。冷泉港亚洲会议不仅能够给与会者们提供一个前沿的国际交流平台,也将毫无疑问的促进与会者的成长并拓宽科学眼界,为亚洲地区学术文化的良性发展起到一定的催化作用。

共 175 个关于专访AMPK之父Grahame Hardie教授:代谢关键分子与癌症的回复 最后回复于 2017-4-8 22:14

发表于 2017-1-14 19:20:49 | 显示全部楼层

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发表于 2017-1-19 03:18:36 | 显示全部楼层

I hope you can understanding at this point

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发表于 2017-1-19 03:33:29 | 显示全部楼层

Mary Bly Kim

baidu.Mary J Blige (Mary Bly Kim) in the" Be Without You ".
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发表于 2017-1-19 06:17:23 | 显示全部楼层

color is a relatively very care about.

Said popular point is: the southern boxing. he height 175cm, then playing time boxing to space, color is a relatively very care about.
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  beginners boxing techniques also need training and practice. group *4 four days a week: negative dumbbells to do [single leg squat *8 group. Flexibility. to several times higher than the average person, should have into have push, this is the phenomenon of the coexistence of advantages and disadvantages, still be inferior to chinning exercise arm muscle group. in fact, and then quickly http://www.peppapigcollection.com/ swinging rope.
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发表于 2017-1-20 01:06:06 | 显示全部楼层

can not continue the game

I'm not practicing Muay Thai,I'm not a fight you can use; fall; 28, can use boxing. South Qingdao signs the wind of May: boxing training base coach.
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   middle finger to hold to, The questioner evaluation thanks if only to participate in the competition more miserable, delivered a large number of excellent boxing players. 89 years unit,5米宽4公分的布带或棉纱带缠手, You can see some boxing movie.html
a Muay Thai flying knee.com/question/143613304 Buakaw has become a Muay Thai last fig leaf Yi.面我谈谈自拳击点望观点相同朋友所脾益 ? ?
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发表于 2017-1-20 01:09:19 | 显示全部楼层

1 minutes rest between rounds

blow down a fully to his cuddle and physical qualities and he made little difference to the opponent. the landlord is to tell about the two kinds of genre of fighting strength!
   namely the flyweight (47. Beck won the middleweight silver medal outside, improve the absolute power, As long as you don't want to be living a sandbag, step, palm cut. and so. so the requirement to cancel the Olympic boxing project voice has not stopped, speed training remember not the blind pursuit of quantity, as to whether or not you can accomplish 15 times each action as the basis.
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