Presence of epidermal haemoglobin may explain skin’s defence against ageing and cancer

19th November 2023

The presence of haemoglobin in the skin’s epidermis has been discovered for the first time, offering insight into the skin’s defence mechanisms against ageing and cancer, researchers have announced.

Published in the Journal of Investigative Dermatology, a team from the Keio University School of Medicine in Tokyo sought to determine candidates for unidentified molecules involved in the barrier mechanism by analysing highly expressed genes in the upper epidermis of both humans and mice.

They conducted a comparative transcriptome analysis of the whole and upper epidermis, both of which were enzymatically separated as cell sheets from human and mouse skin.

They found that the messenger RNA level of haemoglobin α, an oxygen carrier in erythroid cells, was enriched in the upper epidermis compared with the levels in the whole epidermis.

To confirm their findings, they then used immunostaining to visualise the presence of haemoglobin α protein in keratinocytes of the upper epidermis.

The researchers also discovered that epidermal haemoglobin was upregulated by oxidative stress and inhibited the production of reactive oxygen species in human keratinocyte cell cultures.

As haemoglobin binds gases such as oxygen, carbon dioxide, and nitric oxide, and is also an iron carrier via the heme complex, it is therefore thought that epidermal haemoglobin is a prime candidate for antioxidant activity and potentially other roles in barrier function.

Professor Masayuki Amagai was lead investigator of the study and professor in the Department of Dermatology at Tokyo’s Keio University School of Medicine, and the Laboratory for Skin Homeostasis at the RIKEN Center for Integrative Medical Sciences, Yokohama.

He said: ’Our findings suggest that haemoglobin α protects keratinocytes from oxidative stress derived from external or internal sources such as UV irradiation and impaired mitochondrial function, respectively.

’Therefore, the expression of haemoglobin by keratinocytes represents an endogenous defence mechanism against skin aging and skin cancer.’

Professor Amagai added: ’Previous studies have identified the expression of various genes with protective functions in keratinocytes during their differentiation and formation of the outer skin barrier.

’However, other barrier-related genes escaped prior detection because of difficulties obtaining adequate amounts of isolated terminally differentiated keratinocytes for transcriptome analysis.’

Taking vitamin C with iron has no effect on haemoglobin levels

20th November 2020

Vitamin C is a dietary constituent which has been shown to promote iron absorption in the duodenum and upper jejunum.

Oral iron is always oxidised to the Fe3+ state, irrespective of how it is taken and requires an acidic environment for adequate absorption. Vitamin C creates a more acidic environment and can prevent the oxidation of iron to the ferric form. However, whether the common practice of advising that vitamin C is taken alongside iron supplements to enhance iron absorption is beneficial has never been tested.

As a result, for this study a team from the Department of Haematology, Huashan Hospital, Shanghai, China, undertook a randomised, open-label trial in adult patients with newly diagnosed iron-deficiency anaemia (IDA). Participants were given 100mg oral iron tablets plus 200mg of vitamin C or 100 mg of iron alone every 8 hours for a total of 3 months and the authors assessed treatment compliance by determining the number of iron and vitamin tablets returned at the end of the study. Included patients had a haemoglobin level less than 13g/dl for men or less than 12g/dl for women. Although treatment continued for 3 months, the primary outcome measure, the change from baseline in haemoglobin levels, was assessed after two weeks. Secondary outcomes included the increase in serum ferritin after 8 weeks and the haemoglobin level after 4 and 8 weeks.

Findings
A total of 440 patients with a mean age of 38.3 years (96.8% women) were randomised and treatment compliance was 98.2%. The mean baseline haemoglobin level was 8.76g/dl in both groups and serum ferritin, 5.89 in the vitamin C group and 6.34 in the iron only group. After two weeks, the change from baseline in haemoglobin levels was 2.00g/dl in the vitamin C group and 1.84g/dl in the iron only group which was not significant. Similarly, the mean change in serum ferritin levels were 35.75ng/ml vs 34.48ng/ml (vitamin C vs iron only). Furthermore, there were no differences in haemoglobin levels after 2, 4, 6 or 8 weeks. The authors concluded that it is unnecessary to add in vitamin C to the iron regime for patients with IDA.

Reference
Li N et al. The efficacy and safety of vitamin D for iron supplementation in adult patients with iron deficiency anaemia: A randomised clinical trial. JAMA Network Open 2020;3(11):e2023644. doi:10.1001/jamanetworkopen.2020.23644 (R