Parkinsonism-associated protein DJ-1 is an antagonist, not an eraser, for protein glycatioin
Gao, Qingzeng
2022
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Glycation is a spontaneous protein modification associated with aging and human disease. The Parkinson-associated protein DJ-1 is a multi-purpose enzyme that has been reported to have deglycase activity that can reverse glycation in proteins, making it an attractive therapeutic target. In this work, we provide a rigorous evaluation of DJ-1 activity and find that DJ-1 cannot be considered a glycation ... read moreeraser. Instead, DJ-1 functions as a glycation antagonist. Using liquid chromatography mass spectrometry (LC-MS) and western-blotting based deglycation assays, we demonstrate that DJ-1 is unable to remove stable AGEs from protein and peptide substrates glycated with MGO. We further demonstrate that DJ-1 cannot remove even early-stage AGEs, like the bis-hemiaminal MGH- DH, from these substrates. However, concurrent incubation of MGO-treated substrates with DJ-1 did reduce levels of overall glycation. Further experiments revealed that this observed glycation antagonism can be solely attributed to DJ-1’s glyoxalase activity. Though DJ-1 does not possess true deglycase activity, it still plays an important role by mitigating the impact of glycolytic and metabolic stress, thereby minimizing the overall glycation burden.
Thesis (B.S.)--Tufts University, 2022.
Submitted to the Dept. of Chemistry.read less - ID:
- cf95js372
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