Hemoglobin Expression in Nonerythroid Cells: Novel or Ubiquitous?

Abstract

Hemoglobin (Hb) is a major protein involved in transport of oxygen (O2). Red blood cells (RBCs) contain maximum amount of Hb and because of their unique structure and plasticity they transport O2 to various tissues of the body at an optimal concentration. Recently, it has been reported that, apart from RBCs, Hb is also expressed by nonerythroid cells such as epithelial cells of different origin. The cells expressing Hb are from the tissues where maintenance of O2 homeostasis is of paramount importance. Hb expression has been observed in the epithelial cells from human tissues including lungs, neurons, retina, and endometrium. Our group has recently demonstrated that Hb is expressed by the cervicovaginal epithelial cells. We further showed that, apart from maintaining O2 homeostasis, Hb and the peptides derived from it play an indispensable role in the protection of vaginal epithelium by exhibiting antimicrobial activity. In this review, we discuss the significance of Hb expression in vaginal epithelial cells and its role in the recognition of pathogens thereby reducing the risk and/or severity of inflammation and/or infections and the possible mechanism by which Hb exhibits antimicrobial and antioxidative functions.

Brain iron overload following intracranial haemorrhage

“…It is not limited to erythroid cells, but rather it can be expressed in a wide range of glial cells, macrophages and neurons within the central nervous system 32–35. Within neurons, Hb may act as an oxygen reservoir and control mitochondrial function 36. While normally stored intracellularly, Hb is occasionally released from cells during haemolysis.…”

Hemoglobin-Improved Protection in Cultured Cerebral Cortical Astroglial Cells: Inhibition of Oxidative Stress and Caspase Activation

“…The present study reveals that treatment of astrocytes with Hb reduced, in a concentration-dependent manner, intracellular ROS and NO levels, phenomenum, which is likely responsible for a reduction of cell death induced by H 2 O 2 . In agreement with the fact that Hb may protect astrocytes from oxidative stress, it has been demonstrated that (i) Hb strongly scavengers ROS and NO (6), (ii) Hb overexpression prevents H 2 O 2 -induced ROS surproduction and cell death in primary rat mesangial cells (54), and (iii) increasing expression of neuronal Hb prior to hypoxia insult enhances neuronal cell viability by decreasing oxidative stress process (45, 55). It cannot be excluded that peroxidase activity of Hb (56, 57) could be in part responsive for its protective effect against H 2 O 2 .…”

“…Clinical studies have shown that the neuronal Hb expression is reduced in brain of patient with Alzheimer disease, Parkinson disease, or dementia with Lewy Bodies (27). Along these lines, it has been reported that treatment of rat with rotenone, neurotoxin used to reproduce features of Parkinson’s disease (70), induces downregulation of Hb expression in selected neuronal populations, i.e., nigral, cortical, and striatal neurons, associated with an elevation of oxidative stress damages and mitochondria dysfunction (55, 71). In contrast, upregulation of neuronal expression of Hb is accompanied by enhanced resistance to oxidative stress under hypoxic conditions (45).…”

Transcriptional regulation of Hb‐α and Hb‐β through nuclear factor E2‐related factor‐2 (Nrf2) activation in human vaginal cells: A novel mechanism of cellular adaptability to oxidative stress

“…24,30 Hb expression is critical for O 2 transport (Rifkind and Nagababu, 2013). However, this was recently been challenged by many investigators who have proved Hb expression is much more versatile than previously assumed.…”

“…However, this was recently been challenged by many investigators who have proved Hb expression is much more versatile than previously assumed. 24,30 Hb expression is critical for O 2 transport (Rifkind and Nagababu, 2013). 32 Previous studies have shown that besides its function as O 2 carrier, Hb also possesses anti-inflammatory, 33 antioxidant, 34 precursor for antimicrobial peptides (AMPs), 35 sensing and signaling 36,37 and antimicrobial 4,38,39 or may have yet unknown functions.…”