Redox and peroxidase activities of the hemoglobin superfamily: relevance to health and disease

BJ Reeder - Antioxidants & Redox Signaling, 2017 - liebertpub.com
Antioxidants & Redox Signaling, 2017liebertpub.com
Abstract Significance: Erythrocyte hemoglobin (Hb) and myocyte myoglobin, although
primarily oxygen-carrying proteins, have the capacity to do redox chemistry. Such redox
activity in the wider family of globins now appears to have important associations with the
mechanisms of cell stress response. In turn, an understanding of such mechanisms in vivo
may have a potential in the understanding of cancer therapy resistance and
neurodegenerative disorders such as Alzheimer's. Recent Advances: There has been an …
Abstract
Significance: Erythrocyte hemoglobin (Hb) and myocyte myoglobin, although primarily oxygen-carrying proteins, have the capacity to do redox chemistry. Such redox activity in the wider family of globins now appears to have important associations with the mechanisms of cell stress response. In turn, an understanding of such mechanisms in vivo may have a potential in the understanding of cancer therapy resistance and neurodegenerative disorders such as Alzheimer's.
Recent Advances: There has been an enhanced understanding of the redox chemistry of the globin superfamily in recent years, leading to advances in development of Hb-based blood substitutes and in hypotheses relating to specific disease mechanisms. Neuroglobin (Ngb) and cytoglobin (Cygb) have been linked to cell protection mechanisms against hypoxia and oxidative stress, with implications in the onset and progression of neurodegenerative diseases for Ngb and cancer for Cygb.
Critical Issues: Despite advances in the understanding of redox chemistry of globins, the physiological roles of many of these proteins still remain ambiguous at best. Confusion over potential physiological roles may relate to multifunctional roles for globins, which may be modulated by surface-exposed cysteine pairs in some globins. Such roles may be critical in deciphering the relationships of these globins in human diseases.
Future Directions: Further studies are required to connect the considerable knowledge on the mechanisms of globin redox chemistry in vitro with the physiological and pathological roles of globins in vivo. In doing so, new therapies for neurodegenerative disorders and cancer therapy resistance may be targeted. Antioxid. Redox Signal. 26, 763–776.
Mary Ann Liebert