Abnormal nitration and S-sulfhydration modification of Sp1-CSE-H2S pathway trap the progress of hyperhomocysteinemia into a vicious cycle
| Autor: | Wen Wang, Yan Li, Ye Wu, Wenjing Yan, Ke Xue, Shangyue Zhang, Huirong Liu, Jiayin Chai, Yan Cao, Dengyu Ji, Chenghua Luo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Specificity protein 1 medicine.medical_specialty Hyperhomocysteinemia business.industry Cystathionine γ lyase equipment and supplies medicine.disease Biochemistry 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Endocrinology chemistry Physiology (medical) Internal medicine Nitration parasitic diseases medicine business 030217 neurology & neurosurgery |
| Zdroj: | Free Radical Biology and Medicine. 164:20-33 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2020.12.440 |
| Popis: | Sp1-CSE-H2S pathway plays an important role in homocysteine-metabolism, whose disorder can result in hyperhomocysteinemia. H2S deficiency in hyperhomocysteinemia has been reported, while the underlying mechanism and whether it in turn affects the progress of hyperhomocysteinemia are unclear. This study focused on the post-translational modification of Sp1/CSE and revealed four major findings: (1) Homocysteine-accumulation augmented CSE's nitration, inhibited its bio-activity, thus caused H2S deficiency. (2) H2S deficiency inhibited the S-sulfhydration of Sp1, down-regulated CSE and decreased H2S further, which in turn weakened CSE's own S-sulfhydration. (3) CSE was S-sulfhydrated at Cys84, Cys109, Cys172, Cys229, Cys252, Cys307 and Cys310, among which the S-sulfhydration of Cys172 and Cys310 didn't affect its enzymatic activity, while the S-sulfhydration of Cys84, Cys109, Cys229, Cys252 and Cys307 was necessary for its bio-activity. (4) H2S deficiency trapped homocysteine-metabolism into a vicious cycle, which could be broken by either blocking nitration or restoring S-sulfhydration. This study detected a new mechanism that caused severe hyperhomocysteinemia, thereby provided new therapeutic strategies for hyperhomocysteinemia. |
| Databáze: | OpenAIRE |
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