University of Oregon researchers have found an unexpected regulatory link between cellular responses to hypoxia and heat shock. Central to the discovery is a gene known as Hypoxia-Inducible Factor-1 (HIF-1) that is critical for both normal and pathological changes, making it a potential target for both health promotion and cancer therapies.
In their study, researchers used microarray technology to observe the activity of genes found in the genome of the fruit fly (Drosophila). With it, they watched as the activity of heat shock proteins was turned on under conditions of low oxygen, or hypoxia. A microarray allows researchers to place tens of thousands of genes on 1.5-inch-square slides and study them under a microscope.
"These are proteins that were previously known to turn up under conditions of heat shock," said Eric Johnson, a professor in the UO Institute of Molecular Biology. "Now they are coming into view in hypoxia conditions as well."
When Johnson's team manipulated the genes to knock out the activity of HIF-1, the change dramatically lowered the presence of heat shock proteins. Over-activation of HIF-1 is often seen in a wide variety of cancers.
"We've found that there is more complexity to how a cell responds to a change in the environment than what we had long suspected," he said. "Instead of having a simple sensing and response process, there are sensing, calibrations, fine-tuning and responses that occur. These connections can now be targeted for therapies."
The findings of the research, which was supported by an American Cancer Society Research Scholar Grant to Johnson, appear online in advance of regular publication in the Journal of Biological Chemistry.
"This HIF-1 activity was somewhat surprising, because people in the past have often thought that these different pathways that sense environmental change have been separate entities," Johnson said. "It has been assumed that different pathways responded to different conditions, but we've found that the regulator of low oxygen response, HIF-1, actually goes over and cranks up the regulator to the heat shock response."
Understanding and targeting the role of HIF-1 could prove beneficial in turning away oxygen from cancerous cells, choking them off by not allowing oxygen in, Johnson said. The rush of oxygen back into cells after a period of hypoxia also works against wound healing.
In healthy cells, the researchers theorize, HIF-1's turning on of heat shock proteins is beneficial, because the proteins appear to prepare the cell for the return of oxygen, which can cause proteins in the cell to unfold. The heat shock proteins activated by HIF-1 help to refold proteins to ensure a healthy cellular response. "It's a very clever system," Johnson said. "Instead of targeting one of the heat shock proteins, we should consider targeting HIF-1, which controls all of their activity during hypoxia."
Jim Barlow | EurekAlert!
Oestrogen regulates pathological changes of bones via bone lining cells
28.07.2017 | Veterinärmedizinische Universität Wien
Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
Spectrally narrow x-ray pulses may be “sharpened” by purely mechanical means. This sounds surprisingly, but a team of theoretical and experimental physicists developed and realized such a method. It is based on fast motions, precisely synchronized with the pulses, of a target interacting with the x-ray light. Thereby, photons are redistributed within the x-ray pulse to the desired spectral region.
A team of theoretical physicists from the MPI for Nuclear Physics (MPIK) in Heidelberg has developed a novel method to intensify the spectrally broad x-ray...
Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.
Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...
Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers
Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...
Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.
At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...
3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects
A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...
26.07.2017 | Event News
21.07.2017 | Event News
19.07.2017 | Event News
28.07.2017 | Health and Medicine
28.07.2017 | Power and Electrical Engineering
28.07.2017 | Life Sciences