A Review on Hemeoxygenase-2: Focus on Cellular Protection and Oxygen Response
Schematic representation of (a) enzimatic activity regulation; (b) redox regulation of HO-2 and BKCa channel. (a) Posttranslational modifications of HO-2 such as Ser 79 phosphorylation via PKC/CK2 can be activated by Glutamate/Ca2+, increasing HO-2 enzimatic activity. CaM/Ca2+ complex also can increase HO-2 activity through interaction between CaM and HO-2 due to an increase of Ca2+ by Glutamate. PTK may increase the activity of HO-2. (b) HO-2 and BKCa constitute a universal oxygen sensor system. Normoxic conditions: BKCa channel opens because inhibitor heme has dissociated from the channel or because CO generated by HO-2 is bound. In hypoxic conditions, CO levels are low and heme is bound to channel, hence BKCa is closed. Thus, heme is bound to HO-2 under normoxic conditions and to the HBD of the BKCa channel under hypoxia. Based on hypothesis proposed by Yi and Ragsdale 2007  Williams et al. 2004 ; see text for details. BKCa channel: voltage- and -activated large conductance K+ channel; CaM: calmodulin; CK2: Casein Kinase 2; PKC: Protein Kinase C; and PTK: Protein Tyrosine Kinase.
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