Heme Oxygenase 1 (HO-1) is an enzyme in endoplasmic reticulum that belongs to the heme oxygenase family. HO-1 cleaves the heme ring at the alpha methene bridge to form Biliverdin. Biliverdin is subsequently converted to Bilirubin by Biliverdin reductase. In physiological state, the highest activity of HO-1 is found in the spleen, where senescent erythrocytes are sequestrated and destroyed. HO-1 activity is highly inducible by its substrate heme and by various non-heme substances such as heavy metals, bromobenzene, endotoxin, oxidizing agents and UVA. HO-1 is involved in the regulation of cardiovascular function and response to a variety of stressors. Defects in HO-1 are the cause of Heme Oxygenase 1 deficiency, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues.
Homeobox protein Hox-A1 is a transcription factor encoded by HOXA1 gene. This gene is one of the four types of homeobox genes each of which contains a homobox DNA sequence that codes for the homeodomain, a region of 60 amino acids responsible for the DNA binding exhibited by these homeobox proteins. These Homeobox genes are essential metazoan genes as they determine the identity of embryonic regions along the anterio-posterior axis. The homeobox protein Hox-A1 may be involved in the placement of hindbrain segments in the proper location along the anterior-posterior axis during development. Early in its development, the vertebrate hindbrain is transiently subdivided into a series of compartments called rhombomeres. Genes have been identified whose expression patterns distinguish these cellular compartments. Two of these genes, Hoxa1 and Hoxa2, have been shown to be required for proper patterning of the early mouse hindbrain and the associated neural crest. It has been detected HOXA1 expression in a variety of human breast cancer lesions, suggesting that HOXA1 may be required for the establishment of breast cancer cells phenotype.
Homeobox B4 (HOXB4) is encoded by the HOXB4 gene which is a member of the the class I homeobox (HOX) gene family and encodes a nuclear protein with a homeobox DNA-binding domain. These genes are master control regulators of developmental programs including embryonic and adult hematopoiesis. Multiple HOX genes, including HOXB4, are highly expressed in the hematopoietic stem cells (HSC) compartment. HOXB4 gene can act in opposite ways when expressed by different cells, promoting the proliferation of stem cells whilst activating the apoptotic pathway in some embryonic structures. The protein HOXB4, as a homeodomain transcription factor, has been shown to be an important regulator of stem cell renewal and hematopoiesis. Incellular or ectopic expression of HOXB4 expands hematopoietic stem and progenitor cells in vivo and in vitro, making it a potential candidate for therapeutic stem cell expansion.
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