Featured Research

from universities, journals, and other organizations

Yeast Finding Links Processes In Heart Disease And Cancer

Date:
April 5, 2005
Source:
Johns Hopkins Medical Institutions
Summary:
By studying a little-known yeast too primitive to get diseases, Johns Hopkins researchers have uncovered a surprising link between two processes at play in heart disease and cancer in people.

By studying a little-known yeast too primitive to get diseases, Johns Hopkins researchers have uncovered a surprising link between two processes at play in heart disease and cancer in people.

Related Articles


In experiments with yeast known as S. pombe, the researchers discovered that a gene that helps the organism make cholesterol also helps it survive when oxygen is scarce. The finding, described in the March 25 issue of Cell, offers a new strategy for killing infectious yeast, but it also suggests that cells' efforts to make cholesterol and detect oxygen levels might be connected in people, too.

"We were simply trying to establish that this yeast could be a model for studying cholesterol-related activities in human cells," says the study's leader, Peter Espenshade, Ph.D., assistant professor of cell biology in Johns Hopkins' Institute for Basic Biomedical Sciences. "We certainly didn't expect to find a completely new role for this gene."

It's already well established that human cells can both make cholesterol and sense oxygen. In people, high levels of cholesterol in the blood are a major risk factor for heart disease, and many human cancer cells are able to survive despite being in tumors' oxygen-starved centers.

"We don't know yet whether cholesterol production and oxygen sensing are connected in human cells, but now we're trying to find out," says Espenshade.

In people, the gene in question, known as SREBP, controls other genes whose products help make or import cholesterol. Cholesterol-lowering drugs called statins mimic this gene's natural role by triggering cells to import more cholesterol, clearing the artery-clogging stuff from the blood.

Despite the obvious medical relevance of SREBP, no one had ever looked at the equivalent system -- or even determined whether there was one -- in yeast, the simple, single-celled relatives with which we share many genes. Because yeast can be easily manipulated and studied, Espenshade figured they might be a good model for figuring out exactly how SREBP is turned on, what it does and how it's shut off -- if the organism has an equivalent process.

Turning first to databases of the entire genetic sequences of various yeast, Espenshade sought yeast genes that looked like SREBP and its binding partner SCAP. Nothing turned up in the well-studied S. cerevisiae, or brewer's yeast, but S. pombe seemed to have the right stuff.

Graduate student Adam Hughes then examined the role of these similar genes to prove that they in fact duplicate the human process. Indeed, the yeast gene they called sre1 triggered activation of cholesterol-producing genes, aided by a gene called scp1 that behaves like SCAP.

As in humans, sre1 somehow gets turned on when cholesterol levels are low, increasing the cell's production of cholesterol. As cholesterol builds up in the cell, sre1 is gradually turned off.

"Essentially, SREBP and sre1 both try to maintain an optimal level of cholesterol in the cells," says Espenshade.

But, based on what he now knows, Espenshade suspects that the yeast use cholesterol levels to figure out whether there's enough oxygen around for biology as usual. Single-celled yeast can alter their biology to live without oxygen, and human cells can do so to a certain extent. Johns Hopkins researcher Gregg Semenza, M.D., Ph.D., discovered a number of years ago how human cells react to low oxygen levels, but that process has never been connected to cholesterol production.

"Our cells can adjust to lowered oxygen by turning on a specific set of genes when oxygen levels drop [using a gene called HIF1-alpha]," says Espenshade. "While there's no known connection between this process and cholesterol production, our results in the yeast suggest that perhaps SREBP itself, or something in the cholesterol pathway, might also serve as an oxygen sensor for mammalian cells."

It makes sense, he says, that the yeast could use its cholesterol levels as an indirect measure of oxygen levels. The cell uses a few oxygen molecules each time it makes cholesterol, so lowered cholesterol levels could signal that there's not enough oxygen around to make it. And because low cholesterol levels automatically turn on the yeast's version of SREBP, it's an easy solution to have the same gene sound the alarm that the cell needs to adapt to low levels of oxygen.

Espenshade says sre1's role in the yeast's production of cholesterol (actually a similar molecule called ergosterol) and sensing of oxygen might offer a new opportunity to kill infectious yeast and fungi that share the gene with S. pombe.

"Without the sre1 gene, the yeast in our experiments died in low oxygen conditions," says Espenshade. "Because low oxygen levels are common in infected tissues, if we can block infectious yeasts' SREBP pathway without affecting human cells' cholesterol pathways, we might be able to treat certain infections."

Espenshade and his team have found that infection-causing yeast Aspergillus, Neurospora, Cryptococcus and Ustilago share S. pombe's cholesterol-related genes, while S. cerevisae and the yeast Candida do not.

The researchers were funded by the National Institute of General Medical Sciences, the National Heart, Lung and Blood Institute and the Burroughs Wellcome Fund. Authors on the paper are Hughes, Bridget Todd and Espenshade, all of Hopkins. Hughes and Todd are both graduate students in the Biochemistry, Molecular and Cell Biology program.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "Yeast Finding Links Processes In Heart Disease And Cancer." ScienceDaily. ScienceDaily, 5 April 2005. <www.sciencedaily.com/releases/2005/03/050329144215.htm>.
Johns Hopkins Medical Institutions. (2005, April 5). Yeast Finding Links Processes In Heart Disease And Cancer. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2005/03/050329144215.htm
Johns Hopkins Medical Institutions. "Yeast Finding Links Processes In Heart Disease And Cancer." ScienceDaily. www.sciencedaily.com/releases/2005/03/050329144215.htm (accessed October 31, 2014).

Share This



More Health & Medicine News

Friday, October 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Melafind: Spotting Melanoma Without a Biopsy

Melafind: Spotting Melanoma Without a Biopsy

Ivanhoe (Oct. 31, 2014) The MelaFind device is a pain-free way to check suspicious moles for melanoma, without the need for a biopsy. Video provided by Ivanhoe
Powered by NewsLook.com
Battling Multiple Myeloma

Battling Multiple Myeloma

Ivanhoe (Oct. 31, 2014) The answer isn’t always found in new drugs – repurposing an ‘old’ drug that could mean better multiple myeloma treatment, and hope. Video provided by Ivanhoe
Powered by NewsLook.com
Chronic Inflammation and Prostate Cancer

Chronic Inflammation and Prostate Cancer

Ivanhoe (Oct. 31, 2014) New information that is linking chronic inflammation in the prostate and prostate cancer, which may help doctors and patients prevent cancer in the future. Video provided by Ivanhoe
Powered by NewsLook.com
Sickle Cell: Stopping Kids’ Silent Strokes

Sickle Cell: Stopping Kids’ Silent Strokes

Ivanhoe (Oct. 31, 2014) Blood transfusions are proving crucial to young sickle cell patients by helping prevent strokes, even when there is no outward sign of brain injury. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins