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| Status |
Public on May 15, 2023 |
| Title |
Transcriptome profile analysis reveals putative molecular mechanisms of 5-aminolevulinic acid toxicity |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Acute hepatic porphyrias (AHPs) are inherited metabolic diseases characterized by decreased activity or reduction in synthesis of the heme biosynthetic pathway enzymes, leading to acute attacks of abdominal pain, hypertension, neuropsychiatric alterations, and a long-term increase in the incidence of hepatocellular carcinoma (HCC). 5-aminolevulinic acid (ALA) seems to be the major pathogenic factor of AHPs. Studies only reported biological effects on specific macromolecules, thus we investigated the global transcriptional changes and perturbed molecular pathways in HepG2 cells following exposure to ALA 2.5 mM or 25 mM for 2 h and 24 h using DNA microarray. The identification and analysis of differentially expressed genes (DEGs) showed distinct transcriptome profiles from each ALA treatment. Molecular pathways and biological processes enrichment analysis of DEGs by KEGG, Reactome, Metacore, and Gene Ontology, showed that ALA ‘2.5 mM-2h’ induced perturbation in the mitochondrial respiratory chain, ion homeostasis, cell proliferation/apoptosis, and UPR/ER stress, which were connected by the network hubs AP1, C/EBP, ATF-6. ALA ‘25 mM-24h’ elicited changes in oxidative stress, cell death/survival, immune response, drug detoxification, and carcinogenesis with AP-1, C/EBP, EGR1, STAT5, Cyclin D1, JAK2, ERK1/2, and RAC1 as the main network hubs and SQSTM1, HMOX1, SPP1, and LONP-1 genes as putative effectors. This study contributes to revealing molecular mechanisms of ALA potentially associated with the pathogenesis of the clinical manifestations of AHPs.
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| Overall design |
Two-condition experiment, ALA 2.5 mM - 2 h vs. Control cells, ALA 2.5 mM - 24 h vs. Control cells, ALA 25 mM - 2 h vs. Control cells, ALA 25 mM - 24 h vs. Control cells. Biological replicates: 4 '2.5 mM 2 h' replicates, 4 '2.5 mM 24 h' replicates, 4 '25 mM 2 h' replicates, 4 '25 mM 24 h' replicates.
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| Web link |
https://www.sciencedirect.com/science/article/pii/S0003986123000395
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| Contributor(s) |
Menezes PR, Trufen CE, Lichtenstein F, Pellegrina DV, Reis EM, Onuki J |
| Citation(s) |
36746260 |
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| Submission date |
May 20, 2022 |
| Last update date |
Aug 14, 2023 |
| Contact name |
Janice Onuki |
| E-mail(s) |
janice.onuki@butantan.gov.br
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| Phone |
+55 11 97304-0447
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| Organization name |
Butantan Institute
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| Street address |
Av. Vital Brasil, 1500 - Butantã
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| City |
São Paulo |
| State/province |
SP |
| ZIP/Postal code |
05503-900 |
| Country |
Brazil |
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| Platforms (1) |
| GPL20844 |
Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Feature Number Version] |
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| Samples (16)
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| GSM6171963 |
2.5mM ALA treatment, harvest at 24h Replicate 1 |
| GSM6171964 |
2.5mM ALA treatment, harvest at 24h Replicate 2 |
| GSM6171965 |
2.5mM ALA treatment, harvest at 24h Replicate 3 |
| GSM6171966 |
2.5mM ALA treatment, harvest at 24h Replicate 4 |
| GSM6171967 |
25mM ALA treatment, harvest at 24h Replicate 1 |
| GSM6171968 |
25mM ALA treatment, harvest at 24h Replicate 2 |
| GSM6171969 |
25mM ALA treatment, harvest at 24h Replicate 3 |
| GSM6171970 |
25mM ALA treatment, harvest at 24h Replicate 4 |
| GSM6171971 |
2.5mM ALA treatment, harvest at 2h Replicate 1 |
| GSM6171972 |
2.5mM ALA treatment, harvest at 2h Replicate 2 |
| GSM6171973 |
2.5mM ALA treatment, harvest at 2h Replicate 3 |
| GSM6171974 |
2.5mM ALA treatment, harvest at 2h Replicate 4 |
| GSM6171975 |
25mM ALA treatment, harvest at 2h Replicate 1 |
| GSM6171976 |
25mM ALA treatment, harvest at 2h Replicate 2 |
| GSM6171977 |
25mM ALA treatment, harvest at 2h Replicate 3 |
| GSM6171978 |
25mM ALA treatment, harvest at 2h Replicate 4 |
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| Relations |
| BioProject |
PRJNA840868 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE203437_RAW.tar |
103.9 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE203437_re_annotated_limma_p_values_24h_25.tsv.gz |
1.2 Mb |
(ftp)(http) |
TSV |
| GSE203437_re_annotated_limma_p_values_24h_2_5.tsv.gz |
1.3 Mb |
(ftp)(http) |
TSV |
| GSE203437_re_annotated_limma_p_values_2h_25.tsv.gz |
1.2 Mb |
(ftp)(http) |
TSV |
| GSE203437_re_annotated_limma_p_values_2h_2_5.tsv.gz |
1.3 Mb |
(ftp)(http) |
TSV |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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