| Autor: |
Lucia Coppo, Simona Scheggi, Graziella DeMontis, Raffaella Priora, Simona Frosali, Antonio Margaritis, Domenico Summa, Danila Di Giuseppe, Monica Ulivelli, Paolo Di Simplicio |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Antioxidantsredox signaling. |
| ISSN: |
1557-7716 |
| Popis: |
Increased plasma concentrations of total homocysteine (tHcy) (mild-moderate hyperhomocysteinemia: 15-50 µM tHcy) are considered an independent risk factor for onset/progression of various diseases, but it is not known how the increase in tHcy causes pathological conditions.Reduced Hcy (HSH ~1% of tHcy) is presumed to be toxic, unlike homocystine (~9%) and HSS-ALB (Hcy-albumin mixed disulfide, ~90%). This and other notions make it difficult to explain the pathogenicity of Hcy because: i) lowering tHcy does not improve pathological outcomes; ii) damage due to HSH usually emerges at supraphysiological doses; iii) it is not known why tiny increments in plasma concentrations of HSH can be pathological. Critical Issue: Albumin may have a role in Hcy toxicity because HSS-ALB could release toxic HSH via thiol-disulfide exchange reactions in cells. Similarly, thiol-disulfide exchange processes of reduced albumin (HS-ALB) or N-homocysteinylated albumin are plausible alternatives for initiating Hcy pathological events. Adverse effects of albumin and other data reviewed here suggest the hypothesis of a role of albumin in Hcy toxicity.HSS-ALB might be involved in disruption of the antioxidant/oxidant balance in critical tissues (brain, liver, kidney). Since homocysteine-albumin mixed disulfide is a possible intermediate of thiol-disulfide exchange reactions, we suggest that homocysteinylated albumin could be a new pathological factor, and that studies on the redox role of albumin and mixed disulfide production via thiol-disulfide exchange reactions could offer new therapeutic insights for reducing Hcy toxicity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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