Health

Mount Sinai Scientists Unlock Secrets of Red Blood Cell Transporter, Potentially Paving the Way for New Drugs

Published

12 months ago

October 29, 2023

A detailed image of the bicarbonate transporter AE1 shows how bicarbonate attaches to the protein. This helped the researchers create a drug-like molecule that could stop bicarbonate transport, which could potentially be used for new treatments for blood disorders.

Newswise — New York, NY—Researchers at the Icahn School of Medicine at Mount Sinai have identified the structure of a special transporter found in red blood cells and how it interacts with drugs. Details on the findings, which were reported in the September 7 issue of Nature Structural & Molecular Biology [DOI: 10.1038/s41594-023-01085-6], could lead to the development of more targeted medicines.

The research team, led by Daniel Wacker, PhD, Bin Zhang, PhD, and Avner Schlessinger, PhD, found that this transporter facilitates the movement of a substance called bicarbonate, which certain drugs can inhibit. They discovered how these drugs block the transporter and devised novel compounds capable of achieving the same effect.

“Our findings provide a detailed understanding of how bicarbonate transporters work, and the newly identified tool compounds open doors to studying conditions involving red blood cells, including hemolytic anemias,” says Dr. Wacker, corresponding author and an Assistant Professor of Pharmacological Sciences, Neuroscience, and Genetic and Genomic Sciences at Icahn Mount Sinai.

Previously, human bicarbonate transporters were poorly understood, despite being involved in many aspects of human physiology, including regulating pH that involves keeping the level of acidity within a specific range.

Using cryo-electron microscopy, the team identified high-resolution structures revealing bicarbonate and inhibitor binding, and their impact on the transport mechanism. With these insights, the researchers used computer simulations to analyze millions of compounds that could interact with the substrate binding site.

Their experiments pinpointed a group of innovative chemical inhibitors specifically designed for anion exchanger 1, a protein that is crucial for maintaining the proper function of the blood and red blood cells.

“Our study also demonstrates the potential for developing new inhibitors with medical potential for other solute carrier (SLC) proteins, a protein family gaining importance in drug development,” says co-author Dr. Zhang, the Willard T.C Johnson Research Professor of Neurogenetics and Director of the Mount Sinai Center for Transformative Disease Modeling at Icahn Mount Sinai.

Next, the researchers plan to expand their studies to other SLC proteins involved in a variety of disorders including neurodegenerative diseases, psychiatric maladies, and cancer.

“This study effectively paves the way to using atomic-level insights toward the rapid development of promising drug-like molecules for SLC proteins,” says co-author Dr. Schlessinger, Associate Professor of Pharmacological Sciences and Associate Director of the Mount Sinai Center for Therapeutics Discovery at Icahn Mount Sinai.

The paper is titled “Substrate binding and inhibition of the anion exchanger 1 transporter.”

Additional co-authors, all with Icahn Mount Sinai except where indicated, are Michael J. Capper, PhD; Shifan Yang, PhD; Alexander C. Stone; Sezen Vatansever, MD, PhD (Amgen); Gregory Zilberg, PhD Candidate; Yamuna Kalyani Mathiharan, PhD; Raul Habib, (University of California, Berkeley);

Keino Hutchinson, PhD; Yihan Zhao, PhD Candidate; Mihaly Mezei, PhD; and Roman Osman, PhD.

The project was supported by National Institutes of Health grants R35GM133504, R01GM108911, U01AG046170, RF1AG057440, R01AG068030, R01DK073681, R01DK067555, R01DK061659, T32GM062754, T32DA053558, as well as a Sloan Research Fellowship in Neuroscience, an Edward Mallinckrodt, Jr. Foundation Grant, and a McKnight Foundation Scholars Award.

Source: Mount Sinai Health System

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Related Topics:Blood Disorders health and wellness Hemolytic Anemias Red Blood Cell Transporter

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How Women Can Break the Cycle of Spiraling Before Bedtime

Published

1 day ago

October 21, 2024

Daily News Staff

(Family Features) Sleep is a priority for holistic health, but many women aren’t getting enough of it. Not only does it affect your overall health, but stress-related sleep loss also makes it difficult to maintain focus and energy throughout the day.

Sleep Habits for Women

Nearly half (45%) of women ages 40-60 lose more than two hours of sleep each night due to spiraling thoughts with 10% reporting losing more than four hours of sleep, according to Natrol’s Sleep Spiral Survey, revealing challenges women in this age range face for achieving quality sleep.

“Busy women often struggle with sleep due to lingering stress and anxiety from managing work, family and personal responsibilities, which can lead to spiraling thoughts, keeping the mind active at night,” said Dr. Shelby Harris, a sleep expert and director of sleep at Sleepopolis.

According to survey participants, personal finances are the top sleep disruptor, with 50% of women citing concerns over money as the primary reason they can’t fall asleep most nights. Additionally, 45% of women cite anxiety about the future often keeping them from falling asleep.

Seasonal factors can also impact a good night’s rest. The holiday season is the most challenging time for sleep, with 51% of women experiencing increased late-night thoughts during this period.

Understanding the cause of your sleep disruption is an important step toward improving your sleeping habits, especially since 1 in 3 women have more difficulty sleeping now than they did one year ago.

Regain control of your sleep with these tips:

Set the scene for sleep. Harris recommends updating your sleep environment for better results.

“Avoid bright light and limit screen time at least an hour before bed and focus on creating a cozy sleep environment that suits your needs for quality rest,” she said. “Choose comfortable bedding, set the room to a cool temperature and incorporate soothing sounds like a white noise machine or fan to set yourself up for a good night’s sleep.”

Establish a consistent bedtime routine. You can teach your body to anticipate bedtime and ease into better sleep. Begin preparing for bed at the same time each night and go through the same ritual. That might include grooming and self-care habits to help you wind down for the night.

Consider a sleep aid supplement. Many women (1 in 4) often simply give up trying to fall asleep when experiencing spiraling thoughts, with 89% at least occasionally giving up on sleep altogether and choosing to get out of bed. Melatonin supplements can help calm the mind before bed so you can fall asleep faster and stay asleep.^† Consider Natrol’s selection of drug-free Melatonin Gummies, which can help manage occasional sleep disruptions and support quality sleep.

Take steps to manage stress. Prioritizing stress relief can benefit your overall health along with helping you get better rest. Engaging in relaxing activities like reading, meditating or listening to music can be especially helpful in the evening to clear and soothe your mind before you head for bed.

Harris recommends talking with your doctor if you’ve tried various sleep hygiene strategies and find you’re still struggling to get restorative sleep.

“You can discuss whether a sleep aid such as melatonin is appropriate for you and align on the right amount and timing to address your sleep concerns,” she said.

Find more ideas to support better sleep health at Natrol.com.

Photo courtesy of Shutterstock

^{†These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.}

SOURCE:
Natrol

Our Lifestyle section on STM Daily News is a hub of inspiration and practical information, offering a range of articles that touch on various aspects of daily life. From tips on family finances to guides for maintaining health and wellness, we strive to empower our readers with knowledge and resources to enhance their lifestyles. Whether you’re seeking outdoor activity ideas, fashion trends, or travel recommendations, our lifestyle section has got you covered. Visit us today at https://stmdailynews.com/category/lifestyle/ and embark on a journey of discovery and self-improvement.

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Lower Your COPD Risk at Any Age

You can lower your COPD risk at any age by quitting smoking, avoiding lung irritants, and managing symptoms early. Protect your lungs for life.

Published

3 days ago

October 20, 2024

Daily News Staff

Lower Your COPD Risk at Any Age

(Family Features) Breathing: You may take it for granted, but your lungs are important, and so is protecting them. No matter how old you are, you can take action to prevent certain lung conditions, like chronic obstructive pulmonary disease, or COPD.

It’s a serious lung disease that makes breathing difficult and gets worse over time. COPD is less common in younger adults, but anyone can have it. People with a genetic condition known as Alpha-1 may have symptoms as early as age 20.

Consider these steps to lower your risk for COPD:

If you smoke, get help quitting. Most people with COPD have a history of smoking. It’s not easy to quit, but your health care provider can share resources to support you.
Try to avoid exposure to lung irritants like air pollution, dusts and chemical fumes. Some occupations put you at higher risk for COPD.

Most people are 40 or older when symptoms start. If you have shortness of breath, coughing, wheezing, chest tightness or fatigue, talk to your health care provider. Tell them about your smoking habits, any family history of COPD and exposure to lung irritants and ask if you should be tested for COPD.

If you have COPD, the sooner you learn how to manage it, the sooner you can start to breathe better.Don’t wait. Protect your lungs for life.

To learn more, visit nhlbi.nih.gov/BreatheBetter.

Watch video to find out how!

SOURCE:
National Heart, Lung and Blood Institute

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Lifestyle

5 Things to Know About Medicare Open Enrollment

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Daily News Staff

Medicare Open Enrollment

(Family Features) Medicare Open Enrollment, which runs from Oct. 15-Dec. 7 each year, is the one time you can review, compare and make changes to your Medicare health and prescription drug plans for the next year. Because plans – and your health – can change, it’s important to compare plans every year. Visit Medicare.gov to see what’s new for 2025, including a $2,000 cap on out-of-pocket costs for covered prescription drugs, get extra help with prescription drug costs and more.