弗吉尼亚大学: 血红蛋白控制一氧化氮的传递

Uuiversity of Virginia New Discovery Helps Explain Blood Pressure Regulation and Healing Power of Sunlight

　

 

　

阳光中的紫外线UVB 和UVA 确实可以导致皮肤细胞的DNA受损，加速皮肤的老化，这是不争的事实。

这个发现解释了阳光神奇的疗愈力量：紫外线UVA 刺激血管内皮细胞释放一氧化氮（NO)，红外线扩张血管，红细胞把一氧化氮输送全身，降低血压和保护心血管

　

 

弗吉尼亚大学医学院的研究人员发现了一种意想不到的机制，即血红蛋白控制一氧化氮的传递，从而为血压调节提供了新的线索。这些发现可能指向一个治疗高血压的新的治疗靶点，并可能对许多器官系统和疾病产生深远的影响。

　

　

 

血红蛋白以其在血液中输送氧气的作用而闻名。但它也能结合一氧化氮(NO)，一种强大的血管扩张器。通过放松平滑肌细胞，一氧化氮扩张血管，降低血压。新的UVA研究显示，在肌内皮连接处有一个完整的系统，即平滑肌和血管壁内皮细胞之间的“桥”，使血红蛋白能够调节一氧化氮的传递，实质上控制血管的大小。

　

　

 

UVA的研究人员惊奇地发现在肌内皮结中发现了血红蛋白。起初，他们认为这是一个错误。“我们不相信。我们认为这是污染。“也许我们的手指上沾了血?”…然后我们开始把2和2放在一起。他们的发现为他们在著名的《自然》杂志上赢得了一席之地。

 

一个意想不到的神秘揭开了

UVA小组从其他研究者那里看到了血红蛋白的报告，他们观察了肌内皮连接。但是，为了完整性起见，它通常是一份清单中的一种蛋白质。然而，UVA的研究人员发现，血红蛋白阿尔法实际上是调节一氧化氮的结合，直接影响血管的大小。“简而言之，我们确实发现它与一氧化氮结合，它可以紧密或松散地结合在一起，”Isakson说。“基本上，我们在这个非常局部的结构中有一个完整的系统来调节一氧化氮传递到平滑肌。”

　

　

 

高血压的原因?

一些高血压的慢性问题，Isakson怀疑，可能是血管壁中血红蛋白含量问题的结果。“对这项研究的影响非常广泛。最直接的是血压调节。“我们正在努力寻找方法，在血管壁中明确地删除血红蛋白，并观察血压的变化。”

 

深远的意义

但是UVA研究人员发现的机制可能在身体的许多其他部位起重要作用，而且可能在许多疾病中起重要作用。“有许多关于血红蛋白和(一氧化氮信号)的零散报告，例如，在肺里，在神经元中，在所有其他地方。也许，只是可能，它和我们在这里展示的非常相似:它们形成了这个大分子复合体，它可以非常严格地调控一氧化氮的传递。

 

“在我们的案例中，我们非常感兴趣的是一氧化氮是如何调节血压和扩张平滑肌的。”但你可以推断出神经元。神经元使用一氧化氮来进行细胞交流。炎症反应，还有一个大问题。一氧化氮有抗炎作用（Anti-inflammatory)。我们在这里进行推断，但如果我们是正确的，如果你能调节这个复合物释放出多少一氧化氮，那么你就可以调节炎症反应。

　

 

自然出版

这一研究结果已在《自然》杂志上发表，并将在即将出版的印刷版上发表。这篇论文由Adam C. Straub、Alexander W. Lohman、Marie Billaud、Scott R. Johnstone、Scott T. Dwyer、Monica Y. Lee、Pamela Schoppee Bortz、Angela K. Best、Linda Columbus、Benjamin Gaston和Brant E. Isakson合著。

　

 

https://s.click.taobao.com/F3ohKNw

　

UVA Discovery Helps Explain Blood Pressure Regulation - Nov 13, 2012

 

 

Researchers at the University of Virginia School of Medicine have shed new light on blood pressure regulation with the discovery of an unexpected mechanism by which hemoglobin controls the delivery of nitric oxide. The findings may point to a new therapeutic target for treating high blood pressure and may have far-reaching implications for many organ systems and illnesses.

 

Hemoglobin is best known for its role in transporting oxygen in the blood. But it also can bind nitric oxide, a powerful vasodilator. By relaxing smooth muscle cells, nitric oxide widens blood vessels, decreasing blood pressure. The new UVA research shows that there is a complete system within the myoendothelial junction - the "bridge" between the smooth muscle and the endothelial cells lining the blood vessel walls - that allows hemoglobin to regulate nitric oxide delivery, essentially controlling the size of the blood vessel.

 

The UVA researchers were surprised to spot hemoglobin alpha in the myoendothelial junction. At first they thought it was a mistake. "We didn't believe it. We thought it was contamination," says Brant Isakson, PhD. "Maybe we had a blood smear on our fingers? ... Then we started to put two and two together." What they found has earned them a place in the pages of the prestigious journal Nature.

 

An unexpected mystery solved

 

The UVA team had seen reports of hemoglobin alpha from other researchers looking at myoendothelial junctions. But it would typically be one protein in a list of many, reported for the sake of completeness. The UVA researchers, however, realized hemoglobin alpha was actually regulating the binding of nitric oxide, directly affecting the size of the blood vessel. "To make a complicated story short, we did find it binds the nitric oxide, and it can bind it very tightly or loosely," Isakson says. "Basically what we have in this very localized structure is a complete system for regulating nitric oxide delivery to the smooth muscle."

 

A cause of high blood pressure?

 

Some chronic problems with high blood pressure, Isakson suspects, may be the result of problems with the amount of hemoglobin in the blood vessel wall."The implications for this research are very widespread. The most immediate thing is blood pressure regulation," Isakson says. "We're trying to find ways to specifically delete hemoglobin alpha in the blood vessel wall and look at blood pressure changes."

 

Far-reaching implications

 

But the mechanism the UVA researchers have identified may play an important role in many other parts of the body, and possibly in many illnesses. "There are all these scattered reports of hemoglobin and [nitrogen oxide signaling] expressed in the lungs, for example, and in neurons, and in all these other places. Maybe, just maybe, it's very similar to what we show here: That they form this macromolecular complex and that can very tightly regulate how much nitric oxide is delivered," Isakson says.

 

"In our case, we're very interested in how that nitric oxide regulates blood pressure and dilates the smooth muscle. But you can extrapolate that to neurons. Neurons use nitric oxide for their cell communication," he says. "Inflammatory responses, there's another big one. Nitric oxide is anti-inflammatory. We're really extrapolating here, but if we are correct, if you can regulate how much nitric oxide is released by this complex, then you can regulate the inflammatory response."

 

Nature publication

 

The findings have been published by Nature online and will appear in a forthcoming print edition. The paper is authored by Adam C. Straub, Alexander W. Lohman, Marie Billaud, Scott R. Johnstone, Scott T. Dwyer, Monica Y. Lee, Pamela Schoppee Bortz, Angela K. Best, Linda Columbus, Benjamin Gaston and Brant E. Isakson.

 

UVA Discovery Helps Explain Blood Pressure Regulation  http://physiology.med.virginia.edu/bloodpressure.html