| Full text | |
| Author(s): |
Menezes, P. R.
[1]
;
Gonzalez, C. B.
[2, 1, 3]
;
DeSouza, A. O.
[1]
;
Maria, D. A.
[1]
;
Onuki, J.
[1]
Total Authors: 5
|
| Affiliation: | [1] Butantan Inst, Lab Mol Biol, Av Vital Brasil 1500, BR-05503900 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508900 Sao Paulo, SP - Brazil
[3] Organismo Invest Judicial, Dept Ciencias Forenses, Secc Toxicol, Heredia - Costa Rica
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | MOLECULAR BIOLOGY REPORTS; v. 45, n. 6, p. 2801-2809, DEC 2018. |
| Web of Science Citations: | 2 |
| Abstract | |
Acute intermittent porphyria (AIP) is a heme pathway disorder caused by a decrease in the activity and synthesis of porphobilinogen deaminase. Thus, the first heme precursor 5-aminolevulinic acid (ALA) accumulates in the liver. Reactive oxygen species (ROS) resulting from ALA oxidation may be correlated to a higher incidence of hepatocellular carcinoma (HCC) in AIP patients. However, the molecular mechanisms of this relationship have not been thoroughly elucidated to date. In this study, we investigated the effect of increasing levels of ALA on the expression of proteins related to DNA repair, oxidative stress, apoptosis, proliferation and lipid metabolism. Primary rat hepatocytes were isolated by the collagenase perfusion method, lipoperoxidation was evaluated by a TBA fluorimetric assay and Western blotting was used to assess protein abundance. The data showed that ALA treatment promoted a dose-dependent increase of p53 expression, downregulation of Bcl-2, HMG-CoA reductase and OGG1 and an increase in lipoperoxidation. There was no alteration in the expression of the transcription factor NF-kappa B, catalase and superoxide dismutase. ALA oxidation products induced protein regulation patterns, suggesting the interconnection of cellular processes, such as the intrinsic pathway of apoptosis, redox homeostasis, cell proliferation, lipid metabolism and DNA repair. This study helps to elucidate the molecular mechanisms of hepatotoxicity mediated by ALA pro-oxidant effects and supports the hypothesis that ALA accumulation correlates with a higher incidence of hepatic carcinogenic events. (AU) | |
| FAPESP's process: | 10/51068-6 - Redox state evaluation of hepatocytes treated with 5-aminolevunic acid |
| Grantee: | Janice Onuki |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 07/01966-5 - Lesions to biomolecules induced by 5-aminolevulinic acid and its derivatives |
| Grantee: | Janice Onuki |
| Support Opportunities: | Regular Research Grants |