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). ISSN 1438-2199, 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-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. © The Author(s) 2024.
| Item Type: | Article |
|---|---|
| Funders: | Fundamental Research Grant Scheme, Ministry of Higher Education, Government of Malaysia, International Centre for Genetic Engineering and Biotechnology [CRP/MYS17-05], Agilent Technologies, Inc (PV018-2017) [FRGS/1/2019/SKK08/UM/02/7] |
| Additional Information: | All Open Access, Hybrid Gold Open Access |
| Uncontrolled Keywords: | Amino Acids; Cytokines; Humans; Hydrogen Peroxide; Interleukin-8; NF-kappa B; Tumor Necrosis Factor-alpha; alanine; dextro amino acid; hydrogen peroxide; immunoglobulin enhancer binding protein; interleukin 8; serine; tumor necrosis factor; amino acid; cytokine; immunoglobulin enhancer binding protein; interleukin 8; tumor necrosis factor; amino acid analysis; apoptosis assay; Article; caspase assay; cell death; controlled study; cytokine release; Hep-G2 cell line; human; human cell; in vitro study; mitochondrial membrane potential; mRNA expression level; protein expression; protein expression level; upregulation; chemistry; metabolism |
| Subjects: | Q Science > QR Microbiology R Medicine > RS Pharmacy and materia medica |
| Divisions: | Faculty of Medicine > Medicine Department Centre of Excellence for Research in AIDS (CERiA) Faculty of Pharmacy > Department of Pharmaceutical Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 11 Jul 2024 04:30 |
| Last Modified: | 11 Jul 2024 04:30 |
| URI: | http://eprints.um.edu.my/id/eprint/44700 |
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