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!
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy