An internal transporter that enables us to use the copper we consume in foods like shellfish and nuts to enable a host of vital body functions also has the essential role of protecting the receptor that enables us to grow new blood vessels when ours become diseased, Medical College of Georgia scientists report.
The findings published in the journal Nature Communications point toward the copper transporter ATP7A as a potential new therapeutic target in treating cardiovascular diseases like heart attack, peripheral artery disease and stroke.
“Our paper is talking about a newly discovered function of ATP7A,” says Dr. Masuko Ushio-Fukai, vascular biologist in MCG’s Vascular Biology Center. “Our paper shows that ATP7A directly binds to the receptor for vascular endothelial growth factor, called VEGFR2, to stabilize it, to regulate the receptor itself,” she says of the receptor that enables us to produce new blood vessels from our existing ones in a process called angiogenesis.
They’ve already shown that in diseases like diabetes, a major risk factor for cardiovascular disease, ATP7A expression is down, degradation of VEGFR2 is up and a healthy copper balance lost, which contributes to many of the problems these patients experience like heart attacks and impaired wound healing, says Dr. Tohru Fukai, vascular biologist and cardiologist in the VBC.
It was those findings that got the co-corresponding authors on the new paper thinking there might be a direct link between ATP7A and VEGF’s receptor.
Endothelial cells line our blood vessels, and VEGF stimulates the proliferation and movement of these cells, which lay the foundation and stimulation for restorative new blood vessels. VEGF receptors on endothelial cells are a starting point for angiogenesis, says Fukai.
In healthy humans, angiogenesis occurs to some extent throughout life, but in conditions like diabetes, when this ability is probably needed most, it’s impaired, the scientists say.
They suspect and are further pursuing that the essential crosstalk they have now discovered between transporter and receptor occurs in aging as well when, as with many body functions and factors, levels of ATP7A naturally begin to decrease.
Next steps in their work include identifying drugs that would increase and stabilize ATP7A levels and consequently the VEGF receptor, Ushio-Fukai says.
The reddish metal copper, an essential micronutrient, has long been known to stimulate the proliferation and migration of endothelial cells — copper prompts new blood vessel growth, and removing copper reduces tumor growth in animal models — and copper concentrations are increased in tissue forming new blood vessels, the scientists say. But just how copper stimulates new blood vessel formation has been unknown, they say.
ATP7A typically resides in the cell’s trans-Golgi network — a sort of bus station inside the cell that sends new proteins out where needed — where it delivers copper to enzymes that need the micronutrient to be activated and functional. These enzymes include superoxide dismutase, which breaks down the harmful byproducts of oxygen use like reactive oxygen species, which play a key role in a variety of conditions like cardiovascular disease and diabetes, as well as lysyl oxidase, which is critical to producing connective tissue in the body and essential to healthy bones, hair and more, Fukai says.
When too much copper accumulates inside the cells, as they have seen in conditions like diabetes, ATP7A also has the job of removing the excess because both too much or too little can be destructive. “Copper is both very toxic and essential,” Fukai notes.
Now the MCG scientists have shown that VEGF coaxes ATP7A out of the trans-Golgi network to the cell membrane where it binds to and stabilizes VEGF’s receptor. They also have shown that loss of ATP7A in endothelial cells promotes formation of autophagosomes, which basically cast a membrane net around whatever items are about to be consumed, and which now target VEGFR2 for degradation. The excess copper that begins to accumulate inside the cell can further hamper helpful angiogenesis.
Essential copper enzymes cannot be activated and also excessive amounts of copper cannot be exported. ATP7A would be one of the therapeutic targets to help correct this.”
Dr. Masuko Ushio-Fukai, Vascular Biologist, MCG’s Vascular Biology Center
The collective findings mean that copper transporter ATP7A is required for new blood vessel formation and for restoring blood flow in ischemic cardiovascular disease, they write.
The fact that copper is essential to angiogenesis was shown decades ago, when it was found that just applying copper to endothelial cells stimulates angiogenesis, Ushio-Fukai says.
There has been some indication copper’s role in angiogenesis worked through ATP7A’s delivery of copper to copper containing enzymes like superoxide dismutase. “Our paper changes this concept,” she says.
Conditions that can trigger ATP7A to move out of the trans-Golgi network are signals like a lot of copper being present in the cytoplasm, a fluid-filled pocket in the cell that holds most its contents including the trans-Golgi network; inadequate oxygen, called hypoxia, being supplied to a tissue, like what occurs in heart and peripheral artery disease; and insulin.
Too much copper inside cells is definitely bad, where it can work like what Fukai calls an “atomic weapon” to vigorously produce destructive free radicals. Without sufficient work by ATP7A to keep copper levels balanced, levels of the metal keep going up while the essential activities of copper containing enzymes decrease.
Although our cells naturally make copper receptors, we have to consume the essential micronutrient itself. Foods high in copper include oysters and other shellfish like lobster and small clams, shitake mushrooms, tofu and soybeans, sweet potatoes, sesame seeds and nuts like cashews and walnuts as well as leafy greens like spinach and kale.
Ash, D., et al. (2021) The P-type ATPase transporter ATP7A promotes angiogenesis by limiting autophagic degradation of VEGFR2. Nature Communications. doi.org/10.1038/s41467-021-23408-1.
Russia Just Launched a New Science Module to the Space Station – Universe Today
The International Space Station (ISS) is about to get a little bigger.
On July 21, the Russian Space Agency launched the station’s newest module into orbit aboard a Proton-M rocket. The module, dubbed Nauka (which means science), is the station’s first new module since 2016, aside from some new docking ports and airlocks. The Nauka module includes several important additions that will enhance the station’s capabilities.
One of Nauka’s primary systems is its guidance and navigation abilities, which will provide additional attitude control capabilities to the ISS. At 13 meters long, the module’s interior contains new research facilities and storage space. The module also provides additional sleeping quarters for station crew. This is an important addition, since the United States recently re-established its human spaceflight capabilities with two new spacecraft: SpaceX’s Crew Dragon capsule, and the upcoming Boeing Starliner, slated for another test flight later this year. The addition of both new vehicles alongside the Russian Soyuz vehicle means that bigger crews can visit the station at once, and Nauka will provide these larger crews with a home.
Nauka is also carrying one other new piece of technology: a robotic arm built by the European Space Agency. A counterpart to the Canadarm 2 already on station, the European arm is 11 meters long and is designed to ‘walk’ around the Russian segment of the ISS (which the Canadarm can’t reach), carrying out repairs and upgrades as necessary.
Nauka’s development was a troubled process, and it has gone through years of problems and delays. It was first built as a backup to the Zarya module – the first component of the ISS ever launched in 1998. Nauka was set to join its twin in orbit in 2007, but failed to launch then, and was delayed again several times for various reasons, including fuel leaks, expired warranties, and most recently, pandemic delays.
In recent months, political tensions have raised questions as to the extent of Russia’s commitment to its partnership role in ISS. Nauka’s launch, at last, provides some concrete evidence that Russia is indeed committed to maintaining its presence on the station, at least in the short term, which is good news for everyone involved.
Unfortunately, Nauka’s launch didn’t go entirely smoothly. Although it reached orbit and its antenna and solar panels deployed as expected, a computer glitch caused its first orbit-raising maneuver to fail. After some troubleshooting, a second attempt at the maneuver appears to have been successfully carried out by backup thrusters on July 22.
If all goes well from here on out, it should take about a week for Nauka to reach the station. The latest update from the Russian Space Agency indicated that the next orbit raising attempt is scheduled for Tuesday July 27.
Plans are still in place to remove the Pirs docking port from the station this week (which will burn up in the atmosphere) to make room for Nauka, suggesting that confidence is high that the module will arrive as planned.
Learn more: Jeff Foust, “Russia launches Nauka module to International Space Station” SpaceNews.
Featured Image: Nauka’s launch on July 21. Roscosmos/NASATV.
Elon Musk's SpaceX lands NASA launch contract for mission to Jupiter's moon Europa – Euronews
Elon Musk’s private rocket company SpaceX was awarded a $178 million (€151 million) launch services contract for NASA’s first mission focusing on Jupiter’s icy moon Europa and whether it may host conditions suitable for life, the space agency said on Friday.
The Europa Clipper mission is due for blastoff in October 2024 on a Falcon Heavy rocket owned by Musk’s company, Space Exploration Technologies Corp, from NASA’s Kennedy Space Center in Florida, NASA said in a statement posted online.
The contract marked NASA’s latest vote of confidence in the Hawthorne, California-based company, which has carried several cargo payloads and astronauts to the International Space Station for NASA in recent years.
In April, SpaceX was awarded a $2.9 billion (€2.46 billion) contract to build the lunar lander spacecraft for the planned Artemis program that would carry NASA astronauts back to the moon for the first time since 1972.
But that contract was suspended after two rival space companies, Jeff Bezos’s Blue Origin and defense contractor Dynetics Inc, protested against the SpaceX selection.
Evidence of life?
The company’s partly reusable 23-story Falcon Heavy, currently the most powerful operational space launch vehicle in the world, flew its first commercial payload into orbit in 2019.
NASA did not say what other companies may have bid on the Europa Clipper launch contract.
The probe is to conduct a detailed survey of the ice-covered Jovian satellite, which is a bit smaller than Earth’s moon and is a leading candidate in the search for life elsewhere in the solar system.
A bend in Europa’s magnetic field observed by NASA’s Galileo spacecraft in 1997 appeared to have been caused by a geyser gushing through the moon’s frozen crust from a vast subsurface ocean, researchers concluded in 2018. Those findings supported other evidence of Europa plumes.
Among the Clipper mission’s objectives are to produce high-resolution images of Europa’s surface, determine its composition, look for signs of geologic activity, measure the thickness of its icy shell and determine the depth and salinity of its ocean, NASA said.
Boeing Starliner Orbital Flight Test 2: Live updates – Space.com
The CST-100 Starliner capsule has passed its flight readiness review (FRR) for the upcoming liftoff, which will kick off the uncrewed Orbital Flight Test 2 (OFT-2) mission to the station, NASA and Boeing representatives announced today (July 22). Read the full story here.
Over the weekend, engineers mated the Starliner spacecraft to its Atlas V rocket, marking a key milestone ahead of the mission’s launch next week. See the photos here.
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