Autoxidation of ascorbate mediates lysine N-pyrrolation. (2nd December 2022)

• Record Type: Journal Article
• Authors: Yoshitake, Jun; Shibata, Takahiro; Chikazawa, Miho; Uchida, Koji
• Is Part Of: Free radical research. Volume 56:Number 11/12(2022)
• Page Start: 749
• Page End: 759
• Publication Date: 2022-12-02
• Subjects: Lysine modification -- pyrrolation -- ascorbate -- autoxidation -- glycolaldehyde; Free radicals (Chemistry) -- Periodicals; Antioxidants -- Periodicals; Vitamin C -- Periodicals; Vitamin E -- Periodicals; 541.224
• DOI: 10.1080/10715762.2023.2174865
• Languages: English
• ISSNs: 1071-5762

Abstract

Abstract: Protein N -pyrrolation, which converts lysine residues to N ε -pyrrole-l -lysine (pyrK), is a naturally occurring covalent modification. The pyrrolated proteins have a unique property of binding to DNA-staining agents, such as SYBR Green I (SG), and anti-DNA antibodies, suggesting a physiologically relevant modification that gives rise to DNA mimic protein. These properties of pyrrolated protein are suggested to be associated with innate and autoimmune responses. Short-chain aldehydes derived from lipid peroxidation are thought to be involved in the formation of pyrK. We now report that similar lysine N -pyrrolation also occurs during the metal-catalyzed oxidation of proteins with ascorbate. When human serum albumin (HSA) was incubated with Fe 2+ /ascorbate in the presence and absence of docosahexaenoic acid, the protein was converted to SG-binding proteins even without the polyunsaturated fatty acid. The formation of SG-binding proteins by Fe 2+ /ascorbate was accompanied by the formation of pyrK, which was also detected in ascorbate-treated hemoglobin. Moreover, the metal-catalyzed oxidation of ascorbate produced the pyrrolation factors, glycolaldehyde and glyoxal. These results and the observations that sera from autoimmune-prone MRL- lpr mice recognized modified proteins with Fe 2+ /ascorbate and with glycolaldehyde/glyoxal suggest that the autoxidation of ascorbate, as well as lipid peroxidation, can be a source of autoantigenic N -pyrrolated proteins. Our findings revealed a possible function of ascorbate as an endogenous source of pyrrolated proteins and suggested that the pyrK residues generated in proteins may play a role in the innate and autoimmune responses associated with the oxidative metabolism of ascorbate.