Yap, Siew Hwei and Lee, Cheng Siang and Zulkifli, Nur Diyana and Suresh, Darshinie and Hamase, Kenji and Das, Kumitaa Theva and Rajasuriar, Reena and Leong, Kok Hoong (2024) d-Amino acids differentially trigger an inflammatory environment in vitro. Amino Acids, 56 (1). p. 6. ISSN 0939-4451, DOI https://doi.org/10.1007/s00726-023-03360-8.
Full text not available from this repository.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-& kcy;B, pro-inflammatory cytokine, TNF-alpha, 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-& kcy;B, TNF-alpha, 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.
| Item Type: | Article |
|---|---|
| Funders: | Fundamental Research Grant Scheme, Ministry of Higher Education, Government of Malaysia (FRGS/1/2019/SKK08/UM/02/7), International Centre for Genetic Engineering and Biotechnology (CRP/MYS17-05), Agilent Technologies, Inc (PV018-2017) |
| Uncontrolled Keywords: | d-Amino acid oxidase; <sc>d</sc>-Serine; <sc>d</sc>-Alanine; Inflammation; TNF-alpha |
| Subjects: | R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Medicine > Medicine Department Centre for Internship & Academic Enrichment (CITRA) Faculty of Pharmacy > Department of Pharmaceutical Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 08 Nov 2024 06:47 |
| Last Modified: | 08 Nov 2024 06:47 |
| URI: | http://eprints.um.edu.my/id/eprint/45663 |
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