Heme Oxygenase-1(HO-1) as a Potential Target for Cytoprotection – A Review

Author(s)

Menezes, F., Sarawade, R.

Author's Affiliation

Abstract

Cytoprotection i.e. protection of cells from harmful agents, physiologic stress and pathologic stimuli is and has always been of prime importance. Heme oxygenase (HO) is an enzyme that can help modulate and protect cellular life. HO is a significant rate-limiting enzyme that metabolizes heme to produce equimolar amounts of Biliverdin, Carbon monoxide (CO) & free iron. In this action, the activity of NADPH-Cytochrome P-450 reductase is required. Biliverdin is then reduced by biliverdin reductase to Bilirubin which protects the cells from oxidative stress by scavenging oxygen free radicals. CO stimulates soluble Guanylate Cyclase (sGC) leading to increased production of cGMP & alters smooth muscle cell activity causing vasodilation. The free iron is sequestered into Ferritin which, when HO expression is elevated, plays a vital role in removing Fe²⁺ from cell. Three isoforms of HO have been identified out of which HO-1 is inducible and HO-2 is constitutively expressed. HO-3 is a pseudogene. Upregulation of HO-1 is controlled by upstream signaling kinases namely extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK (Mitogen-activated protein kinase). Various Transcription factors too have a role in activating the HO-1 gene. HO-1 plays a protective role in many disease states such as Atherosclerosis, Alzheimer’s disease, Parkinson’s disease, Hepatitis etc. The focus of this review is the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect cells from harmful agents.

Keywords

Cytoprotection, Heme Oxygenase-1, Oxidative Stress, Signaling Kinase, Transcription Factors

Cite This Article

Menezes, F., & Sarawade, R. (2014). Heme Oxygenase-1(HO-1) as a Potential Target for Cytoprotection- A Review. International Journal for Pharmaceutical Research Scholars (IJPRS), 3(4), 1-9.