The mycosporine-like amino acids porphyra-334 and shinorine are antioxidants and direct antagonists of Keap1-Nrf2 binding.
The mycosporine-like amino acids porphyra-334 and shinorine are antioxidants and direct antagonists of Keap1-Nrf2 binding.
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DOI：
10.1016/j.biochi.2018.07.020
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发表时间：
2018-11
期刊：
影响因子：
3.9
通讯作者：
Long PF
中科院分区：
文献类型：
--
作者：
Gacesa R;Lawrence KP;Georgakopoulos ND;Yabe K;Dunlap WC;Barlow DJ;Wells G;Young AR;Long PF
类菌孢素氨基酸（MAAs）是典型的蓝藻和海藻产生的吸收紫外线的代谢产物，但它们的性质并不限于直接防晒保护。在此，我们研究了卟啉-334和shinorine的抗氧化活性，并证明这些MAA是细胞保护性Keap 1-Nrf 2途径的潜在激活剂。使用荧光偏振（FP）和热位移测定法测定卟啉-334和Shinorine与Keap 1结合的能力，以检测Keap 1受体拮抗作用。同时，卟啉-334和Shinorine从Keap 1解离Nrf 2的能力也通过测量在UVR暴露之前和之后的原代皮肤成纤维细胞中编码氧化应激防御蛋白的Nrf 2靶向基因的mRNA表达增加来证实。令人惊讶的是，增强的转录调控，只有促进暴露于紫外线诱导的氧化应激后，在细胞中的MAA。此外，通过DPPH自由基淬灭试验测定的卟啉-334和Shinorine的体外抗氧化活性与抗坏血酸相比较低。然而，通过ORAC测定确定的它们通过氢原子转移淬灭自由基的抗氧化能力是显著的。因此，MAA提供抗氧化保护的双重性质可能提供一种前瞻性的化疗策略，以预防或延缓多种退行性衰老疾病的进展。类菌孢素氨基酸（MAAs）是一种天然的紫外线过滤剂，主要存在于海洋物种中。MAA作为Keap 1-Nrf 2结合的拮抗剂，并作为化学猝灭剂。MAAs激活Nrf 2调控的基因，但只有在紫外线照射后。这也导致MMP 1的表达减少，MMP 1是一种与光老化相关的胶原酶。MAAs为细胞如何管理紫外线诱导的氧化应激提供了新的见解。
Mycosporine-like amino acids (MAAs) are UVR-absorbing metabolites typically produced by cyanobacteria and marine algae, but their properties are not limited to direct sun screening protection. Herein, we examine the antioxidant activities of porphyra-334 and shinorine and demonstrate that these MAAs are prospective activators of the cytoprotective Keap1-Nrf2 pathway. The ability of porphyra-334 and shinorine to bind with Keap1 was determined using fluorescence polarization (FP) and thermal shift assays to detect Keap1 receptor antagonism. Concomitantly, the ability of porphyra-334 and shinorine to dissociate Nrf2 from Keap1 was confirmed also by measurement of increased mRNA expression of Nrf2 targeted genes encoding oxidative stress defense proteins in primary skin fibroblasts prior and post UVR exposure. Surprisingly, enhanced transcriptional regulation was only promoted by MAAs in cells after exposure to UVR-induced oxidative stress. Furthermore, the in-vitro antioxidant activities of porphyra-334 and shinorine determined by the DPPH free-radical quenching assay were low in comparison to ascorbic acid. However, their antioxidant capacity determined by the ORAC assay to quench free radicals via hydrogen atom transfer is substantial. Hence, the dual nature of MAAs to provide antioxidant protection may offer a prospective chemotherapeutic strategy to prevent or retard the progression of multiple degenerative disorders of ageing. Mycosporine like amino acids (MAAs) are natural UVR filters found predominantly in marine species. MAAs act as antagonists of Keap1-Nrf2 binding, and as chemical quenchers. MAAs activated Nrf2-regulated genes, but only after UV irradiation. This also led to decreased expression of MMP1, a collagenase linked to photoageing. MAAs offers new insight into how cells can manage UV-induced oxidative stress.
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影响因子：
3.9
作者：
Dinkova-Kostova AT;Baird L;Holmström KM;Meyer CJ;Abramov AY
通讯作者：
Abramov AY
DOI：
10.1073/pnas.0501475102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Devling, TWP;Lindsay, CD;Hayes, JD
通讯作者：
Hayes, JD
影响因子：
16
作者：
Baird, Liam;Swift, Sam;Lleres, David;Dinkova-Kostova, Albena T.
通讯作者：
Dinkova-Kostova, Albena T.
DOI：
10.1073/pnas.172398899
发表时间：
2002-09-03
影响因子：
11.1
作者：
Dinkova-Kostova, AT;Holtzclaw, WD;Talalay, P
通讯作者：
Talalay, P
DOI：
10.1073/pnas.1305687110
发表时间：
2013-09-17
影响因子：
11.1
作者：
Baird, Liam;Lleres, David;Dinkova-Kostova, Albena T.
通讯作者：
Dinkova-Kostova, Albena T.