Cysteine-independent activation/inhibition of heme oxygenase-2
| Autor: | Walter A. Szarek, Kanji Nakatsu, Terence R.S. Ozolinš, Mona N. Rahman, Mahin D. Maines, Zongchao Jia, Dragic Vukomanovic |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Neuroscience (miscellaneous) HO-2 activator Heme degradation heme oxygenase-2 HO-2 inhibitor thiols menadione QC-2350 in vitro Isozyme law.invention lcsh:RD78.3-87.3 03 medical and health sciences chemistry.chemical_compound Menadione law Heme Alanine In vitro Heme oxygenase 030104 developmental biology Anesthesiology and Pain Medicine chemistry Biochemistry lcsh:Anesthesiology Recombinant DNA Cysteine Research Article |
| Zdroj: | Medical Gas Research, Vol 6, Iss 1, Pp 10-13 (2016) Medical Gas Research |
| ISSN: | 2045-9912 |
| Popis: | Reactive thiols of cysteine (cys) residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2) isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2) and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD) and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282. |
| Databáze: | OpenAIRE |
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