Hemoglobin discovery sheds light on skin defense, hair growth and antimicrobial functions

20 Nov 2023 --- A recent study focusing on the epidermis helps explain the activities of hemoglobin alpha (HBA) in this outermost layer of the skin. While this protein is typically found in red blood cells — actively delivering oxygen to cells and tissues throughout the body — findings from the paper uncover its protective functions in the skin barrier. 

Underscoring the complexity of skin biology, the discovery points to potential new pathways to formulating dermatological solutions aimed at fortifying the skin’s natural defenses.

HBA exhibited a notable presence in specific skin cells known as keratinocytes within the stratum spinosum and stratum granulosum layers. Interestingly, HBA was also found in hair follicle keratinocytes, suggesting a potential specialized function in hair-bearing skin regions.

“Emerging evidence suggests that vertebrate hemoglobin has additional functions beyond an oxygen-carrying protein in erythrocytes,” the scientists comment.

“Particularly, terrestrial animals may have acquired promoter activity in their hemoglobin genes as an evolutionary adaptation to cope with reactive oxygen species (ROS) exposure. Our findings provide important insights into ROS-related skin diseases, such as aging and cancers.”

Emerging evidence suggests that hemoglobin has additional functions in skin health maintenance, beyond being an oxygen-carrying protein in the blood.While human genetic disease of hemoglobin — including thalassemia syndromes and sickle cell disorders — reportedly predispose red blood cells to oxidative stress, the researchers note their harmful effects on epidermal skin cells have been unknown.

“Given the ability of hemoglobin to bind to gasses such as oxygen, carbon dioxide and nitric oxide as well as its role as an iron carrier through the heme complex, these properties may have implications for its antioxidant activity and other roles in barrier function,” explain the study authors.

Hemoglobin’s protective activity
To find out which molecules help protect our skin, the researchers looked closely at the genes that are most active in the top layers of the skin. They studied skin samples taken from three healthy individuals’ thighs and upper arms. They separated these samples into different layers and did detailed tests to compare the genes in each layer.

The scientists discovered certain genes were more active in the top layer of the skin compared to the rest.

Some of these genes are markers that reveal activities happening on different layers of the skin. Among these active genes, the researchers found ones related to HBA.

Further tests confirmed that these HBA-related genes are highly active in the upper layers of the skin. It was concluded that these genes are associated with responding to oxidative stress caused by things like the sun’s rays. This suggests they might have a protective role in our skin when it comes to dealing with stress.

When HBA was suppressed, the production of ROS in keratinocytes after UV exposure rose significantly, reinforcing the idea of HBA’s protective role against oxidative damage.

Under such stress, HBA levels were found to have increased, indicating the protein’s potential antioxidant function within the skin.

To confirm their findings, scientists also studied skin cells from mice. It was observed that in mice, hemoglobin was found mainly in the skin that’s regularly exposed to the sun and environment, like the skin on the body’s surface.

Under UV-related stress, hemoglobin levels in the skin were found to have increased, indicating the protein’s potential antioxidant function within the epidermis.However, further research, possibly even with specially engineered mice lacking specific hemoglobin genes in their skin, is needed to fully understand these functions, according to the researchers.

Stimulating hair growth
Interestingly, the researchers discovered that hemoglobin activity was particularly high in certain areas of hair follicles. These areas are important for protecting against harmful microbes, and it appears the presence of hemoglobin might be related to this protective function.

“Because HBA-derived peptides also exhibit bactericidal properties, the prominent HBA expression in the isthmus may be attributed to its functional demand for stem cell protection against the invasion of skin microbiota at the follicular opening,” note the researchers.

Additionally, when skin cells are actively growing, such as during the phase when hair follicles are in a growth period, it was found that the expression of HBA increases. This discovery suggests that HBA might help support the growth of hair in these stages.

Published in the Journal of Investigative Dermatology, this study marks a step forward in comprehending the intricate mechanisms of skin barrier and hair follicle functions, potentially offering valuable insights for skin care advancements.

Earlier this month, skin care Element Eight secured US$6 million funding for its cell oxygenating tech that mimics hemoglobin by delivering 20 times more oxygen directly to skin cells, up to 700 microns deep.

By Benjamin Ferrer