d-Amino acids differentially trigger an inflammatory environment in vitro
Abstract Studies in vivo have demonstrated that the accumulation of d-amino acids (d-AAs) is associated with age-related diseases and increased immune activation. However, the underlying mechanism(s) of these observations are not well defined. The metabolism of d-AAs by d-amino oxidase (DAO) produce...
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| Format: | Article |
| Language: | English |
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Springer
2024-02-01
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| Series: | Amino Acids |
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| Online Access: | https://doi.org/10.1007/s00726-023-03360-8 |
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| author | Siew Hwei Yap Cheng Siang Lee Nur Diyana Zulkifli Darshinie Suresh Kenji Hamase Kumitaa Theva Das Reena Rajasuriar Kok Hoong Leong |
| author_facet | Siew Hwei Yap Cheng Siang Lee Nur Diyana Zulkifli Darshinie Suresh Kenji Hamase Kumitaa Theva Das Reena Rajasuriar Kok Hoong Leong |
| author_sort | Siew Hwei Yap |
| collection | DOAJ |
| description | Abstract Studies in vivo have demonstrated that the accumulation of d-amino acids (d-AAs) is associated with age-related diseases and increased immune activation. However, the underlying mechanism(s) of these observations are not well defined. The metabolism of d-AAs by d-amino oxidase (DAO) produces hydrogen peroxide (H2O2), a reactive oxygen species involved in several physiological processes including immune response, cell differentiation, and proliferation. Excessive levels of H2O2 contribute to oxidative stress and eventual cell death, a characteristic of age-related pathology. Here, we explored the molecular mechanisms of d-serine (d-Ser) and d-alanine (d-Ala) in human liver cancer cells, HepG2, with a focus on the production of H2O2 the downstream secretion of pro-inflammatory cytokine and chemokine, and subsequent cell death. In HepG2 cells, we demonstrated that d-Ser decreased H2O2 production and induced concentration-dependent depolarization of mitochondrial membrane potential (MMP). This was associated with the upregulation of activated NF-кB, pro-inflammatory cytokine, TNF-α, and chemokine, IL-8 secretion, and subsequent apoptosis. Conversely, d-Ala-treated cells induced H2O2 production, and were also accompanied by the upregulation of activated NF-кB, TNF-α, and IL-8, but did not cause significant apoptosis. The present study confirms the role of both d-Ser and d-Ala in inducing inflammatory responses, but each via unique activation pathways. This response was associated with apoptotic cell death only with d-Ser. Further research is required to gain a better understanding of the mechanisms underlying d-AA-induced inflammation and its downstream consequences, especially in the context of aging given the wide detection of these entities in systemic circulation. |
| format | Article |
| id | doaj-art-61d46c25585641e983ed3b4fb8589c12 |
| institution | Kabale University |
| issn | 1438-2199 |
| language | English |
| publishDate | 2024-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Amino Acids |
| spelling | doaj-art-61d46c25585641e983ed3b4fb8589c122024-12-22T12:34:21ZengSpringerAmino Acids1438-21992024-02-0156111310.1007/s00726-023-03360-8d-Amino acids differentially trigger an inflammatory environment in vitroSiew Hwei Yap0Cheng Siang Lee1Nur Diyana Zulkifli2Darshinie Suresh3Kenji Hamase4Kumitaa Theva Das5Reena Rajasuriar6Kok Hoong Leong7Centre of Excellence for Research in AIDS (CERiA), Universiti MalayaCentre of Excellence for Research in AIDS (CERiA), Universiti MalayaDepartment of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains MalaysiaDepartment of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains MalaysiaGraduate School of Pharmaceutical Sciences, Kyushu UniversityDepartment of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains MalaysiaCentre of Excellence for Research in AIDS (CERiA), Universiti MalayaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti MalayaAbstract Studies in vivo have demonstrated that the accumulation of d-amino acids (d-AAs) is associated with age-related diseases and increased immune activation. However, the underlying mechanism(s) of these observations are not well defined. The metabolism of d-AAs by d-amino oxidase (DAO) produces hydrogen peroxide (H2O2), a reactive oxygen species involved in several physiological processes including immune response, cell differentiation, and proliferation. Excessive levels of H2O2 contribute to oxidative stress and eventual cell death, a characteristic of age-related pathology. Here, we explored the molecular mechanisms of d-serine (d-Ser) and d-alanine (d-Ala) in human liver cancer cells, HepG2, with a focus on the production of H2O2 the downstream secretion of pro-inflammatory cytokine and chemokine, and subsequent cell death. In HepG2 cells, we demonstrated that d-Ser decreased H2O2 production and induced concentration-dependent depolarization of mitochondrial membrane potential (MMP). This was associated with the upregulation of activated NF-кB, pro-inflammatory cytokine, TNF-α, and chemokine, IL-8 secretion, and subsequent apoptosis. Conversely, d-Ala-treated cells induced H2O2 production, and were also accompanied by the upregulation of activated NF-кB, TNF-α, and IL-8, but did not cause significant apoptosis. The present study confirms the role of both d-Ser and d-Ala in inducing inflammatory responses, but each via unique activation pathways. This response was associated with apoptotic cell death only with d-Ser. Further research is required to gain a better understanding of the mechanisms underlying d-AA-induced inflammation and its downstream consequences, especially in the context of aging given the wide detection of these entities in systemic circulation.https://doi.org/10.1007/s00726-023-03360-8d-Amino acid oxidased-Serined-AlanineInflammationTNF-α |
| spellingShingle | Siew Hwei Yap Cheng Siang Lee Nur Diyana Zulkifli Darshinie Suresh Kenji Hamase Kumitaa Theva Das Reena Rajasuriar Kok Hoong Leong d-Amino acids differentially trigger an inflammatory environment in vitro Amino Acids d-Amino acid oxidase d-Serine d-Alanine Inflammation TNF-α |
| title | d-Amino acids differentially trigger an inflammatory environment in vitro |
| title_full | d-Amino acids differentially trigger an inflammatory environment in vitro |
| title_fullStr | d-Amino acids differentially trigger an inflammatory environment in vitro |
| title_full_unstemmed | d-Amino acids differentially trigger an inflammatory environment in vitro |
| title_short | d-Amino acids differentially trigger an inflammatory environment in vitro |
| title_sort | d amino acids differentially trigger an inflammatory environment in vitro |
| topic | d-Amino acid oxidase d-Serine d-Alanine Inflammation TNF-α |
| url | https://doi.org/10.1007/s00726-023-03360-8 |
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