Figure 1.

Overview of the predominant mechanisms underlying HO product-mediated cell protection. The two products of HO activity, namely, CO and BV/BR, are associated with the beneficial role of this enzyme. In stimulating cGMP synthesis, CO acts similarly to another gas messenger, NO. It further activates intracellular signaling cascades, involving Nrf2, which provides an anti-oxidative defense, and by interacting with ion channels for modulating glucose metabolism and inhibiting apoptosis. An anti-inflammatory action of BV/BR is predominantly executed by inhibiting generation of reactive oxygen and nitrogen species, via NOX and iNOS. Further, BR/BV possesses potent antioxidant capacity towards oxidation of biomolecules. Recently, BR acts as ligand of PPARα, thereby controlling lipid and energy homeostasis. Solid arrows indicate the most considered protective pathways. Abbreviations: ARE, antioxidant response elements; cGMP, cyclic guanosine monophosphate; iNOS, inducible NO-synthase; Keap, Kelch-like ECH-associated protein 1; Nrf2, nuclear-factor-E2-related factor-2; NO, nitric oxide; Nox4, NADPH oxidase (isoform 4); ROS, reactive oxygen species. PPAR, peroxisome proliferator activated receptor.