Health Scan: How stress controls hemoglobin levels in blood

What role does cellular stress play in the production of hemoglobin?

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April 22, 2017 23:47
4 minute read.
The Hebrew University

The Hebrew University. (photo credit: Wikimedia Commons)

 
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Man’s ability to breathe oxygen, thanks to the hemoglobin in the blood, is critical to our survival. Since air at high altitudes contains less oxygen, the body is under pressure to make hemoglobin rapidly – a stressful activity. But what role does cellular stress play in the production of hemoglobin?

In a paper recently published in the prestigious journal Cell Research, Hebrew University of Jerusalem researchers reported the discovery of an entirely new mechanism through which globin genes are expressed. Discovery of this property of the hemoglobin genes that was unknown until now shows that stress is vital for making possible the production of hemoglobin.

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To produce a globin protein molecule, the DNA of the globin gene is first transcribed into a long RNA molecule from which internal segments must be spliced out to generate the RNA template for protein synthesis in the red cell.

The team of molecular biologists led by molecular biologist and cancer researcher Prof. Raymond Kaempfer in the HU Faculty of Medicine reports that for each of the adult and fetal globin genes, the splicing of its RNA is strictly controlled by an intracellular stress signal.

The signal, which has been known for a long time, involves an enzyme present in every cell of the body, called PKR, which remains “silent” unless it is activated by a specific RNA structure thought to occur only in RNA made by viruses.

The team discovered that the long RNAs transcribed from the globin genes each contain a short intrinsic RNA element that is capable of strongly activating PKR. Unless the PKR enzyme is activated this way, the long RNA cannot be excised to form the mature RNA template for globin protein synthesis.

“Surprisingly, we have revealed an entirely new mechanism through which hemoglobin gene expression is regulated by stress. An intracellular signal, essential for coping with stress, is absolutely necessary to allow for hemoglobin production. That stress signal is activated by the hemoglobin gene itself. Although we have long known that this signal strongly inhibits protein synthesis in general, during hemoglobin gene expression it first plays its indispensable, positive role before being turned off promptly to allow for massive hemoglobin formation needed for breathing,” said Kaempfer.



The team demonstrated a novel, positive role for PKR activation and eIF2-alpha phosphorylation in human globin RNA splicing, in contrast to the long-standing negative role of this intracellular stress response in protein synthesis.

The realization that stress is essential may have important implications for how we understand hemoglobin expression, they explained.

“What this boils down to is that even at the cellular level, stress and the ability to mount a stress response are essential to our survival. We have long known this in relation to other biological processes, and now we see that it is at play even for the tiny molecules that carry oxygen in our blood,” explained Kaempfer.

VR THERAPY HELPS CUT PAIN IN HOSPITAL PATIENTS

Virtual reality therapy is effective in significantly reducing pain for hospitalized patients, according to a study at Cedars-Sinai Medical Center in California. In the study, published in JMIR Mental Health, investigators examined 100 hospitalized patients who reported pain scores of greater than three on the Numeric Pain Rating Scale from zero to 10.

Some 50 patients received virtual reality therapy consisting of wearing virtual reality goggles to watch calming video content, such as helicopter rides over scenic portions of Iceland or imagery of swimming in the ocean with whales. Those patients reported a 24% drop in pain scores after using the virtual reality goggles.

Another 50 patients viewed a standard, two-dimensional nature video, depicting relaxing scenes with a calming music audio track on a close-proximity screen. Although those patients also experienced a reduction in pain, the decrease of 13.2% was less dramatic.

“Results indicate virtual reality may be an effective tool along with traditional pain management protocols,” said Dr. Brennan Spiegel, director of Cedars-Sinai’s Health Service Research. “This gives doctors and patients more options than medication alone.”

While it remains unknown exactly how VR works to reduce pain, Spiegel attributed the benefit to what he calls “immersive distraction” – when the mind is busy in an immersive experience, it becomes difficult, if not impossible, to perceive other stimuli, including pain.

“We believe virtual reality hijacks the senses, but in a good way,” Spiegel said. “It creates an immersive distraction that stops the mind from processing pain, offering a drug-free supplement to traditional pain management.”

STOP EATING

The great Jewish scholar and physician Maimonides always advised getting up from a meal before you are satiated. Now researchers at the Korea Advanced Institute of Science and Technology in Daejeon have identified a molecule sent by fat cells to the fly brain that senses when they have had enough food and inhibits feeding, according to a study published recently in PLOS Biology.

Fat is the primary long-term energy storage molecule in animals, and the control of fat levels is critical for survival.

In mammals, the hormone leptin induces eating in response to fat loss, but so far no corresponding signal has been identified, either in mammals or any other animal, that inhibits eating in response to fat gain. Because fruit flies replicate many of the feeding-related regulatory mechanisms and genes known to operate in humans, they make a good model for the search for such an inhibitory signal.

“Our study indicates that fat tissue sends a molecular signal to the fly brain to regulate feeding behavior, the researchers said.

“Further studies will be needed to determine if a similar system acts in mammals, and if so, whether it can be safely manipulated to help achieve weight loss, or gain, in people.”

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