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Transcriptome profile analysis reveals putative molecular mechanisms of 5-aminolevulinic acid toxicity

ABSTRACT: Transcriptome profile analysis reveals putative molecular mechanisms of 5-aminolevulinic acid toxicity

PROVIDER: PRJNA840868 | ENA |

REPOSITORIES: ENA

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Transcriptome profile analysis reveals putative molecular mechanisms of 5-aminolevulinic acid toxicity

Project description: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.

2023-05-15 | GSE203437 | GEO

Expression data from Arabidopsis thaliana seedlings with reduced synthesis of 5-aminolevulinic acid

Project description:5-aminolevulinic acid (ALA) is the common precursor of all biological synthezised tetrapyrroles. Inhibition of ALA synthesis results in decreased amounts of chlorophylls, heme, siroheme and phytochrome. It was previously shown that 4 out of 5 Arabidopsis mutants uncoupling nuclear gene expression from the physiological state of the chloroplast are affected in plant tetrapyrrole biosynthesis. It is common to all four mutants to show a reduced ALA formation. We investigate the impact of reduced plastidic ALA synthesis on nuclear gene expression by inhibition of ALA formation using gabaculin and compare these effects with the gun4-1 mutant. Formation of 5-aminolevulinic acid was inhibited in Arabidopsis thaliana Col-0 seedlings by application of 10 µM gabaculin. Additionally the Arabidopsis gun4-1 mutant was investigated. Seedlings were etiolated for 3 days on MS medium in absence or presence of gabaculin and subsequently deetiolated for 6 hours. Total RNA was extracted and used for microarray hybridisation.

2011-04-01 | E-GEOD-27704 | biostudies-arrayexpress

Characterization of 5-aminolevulinic acid effects on radiotherapy using mouse tumor model.

2016-08-14 | GSE54718 | GEO

Characterization of 5-aminolevulinic acid effects on radiotherapy using mouse tumor model.

Project description:B16-BL6 mouse melanoma that had been maintained in C57BL/6J mice were used to evaluate the 5-aminolevulinic acid (ALA) effects on radiotherapy. Mice were divided into 4 groups after implantation of B16-BL6 cells; (1) control group; (2) ALA treatment; (3) Xray treatment; (4) ALA and Xray treatment. B16-BL6 mouse melanoma tumor gene expressions in 4 groups were measured after fractionated doses of radiation with local administration of 50mg/kg ALA prior to fractional irradiation.

2016-08-14 | E-GEOD-54718 | biostudies-arrayexpress

The study on laparoscopic diagnosis of peritoneal dissemination of colorectal cancer with 5-aminolevulinic acid

Project description:Interventions: 5 Aminolevulinic acid Primary outcome(s): Positive predictive value in intraoperative photodynamic diagnosis using 5 aminolevulinic acid in colorectal peritoneal dissemination Study Design: Single arm Non-randomized

| 2645701 | ecrin-mdr-crc

Evaluation of 5-aminolevulinic acid-mediated radiodynamic therapy after single-dose irradiation in HT-29 xenografted mice

Project description:We investigated changes in gene expression in HT-29 human colon carcinoma xenografts in nude mice after single-dose X-ray irradiation combined with 5-aminolevulinic acid (ALA)-mediated radiodynamic therapy. Control (non-irradiated, no ALA) and treated tumor samples were analyzed using Aglient Whole Human Genome Microarray 4x44K G4112F.

2025-11-23 | GSE308518 | GEO

Expression data from Arabidopsis thaliana seedlings with reduced synthesis of 5-aminolevulinic acid

2011-04-01 | GSE27704 | GEO

Characterization of 5-aminolevulinic acid and radiation dose effects on radiotherapy using mouse tumor model.

Project description:B16-BL6 mouse melanoma that had been maintained in C57BL/6J mice were used to evaluate the 5-aminolevulinic acid (ALA) and radiation dose effects on radiotherapy. Mice were divided into 6 groups after implantation of B16-BL6 cells; (1) no treatment (NT) ; (2) 5-ALA treatment (ALAT); (3) 10 session of fractionated irradiation (2Gy/day) (20XT); (4) 10 sessions of 5-ALA treatment followed by fractionated irradiation (2Gy/day) (ALA-20XT); (5) 10 session of fractionated irradiation (3Gy/day) (30XT); (6) 10 sessions of 5-ALA treatment followed by fractionated irradiation (3Gy/day) (ALA-30XT).

2018-02-01 | GSE92972 | GEO

Clinical research of diagnosis for lymph node metastases of gastrointestinal cancer by using 5-aminolevulinic acid

Project description:Interventions: Oral administration of 5-aminolevulinic acid before surgery Primary outcome(s): evaluation of the diagnosis rate of the lymph node metastasis Study Design: Single arm Non-randomized

| 2620522 | ecrin-mdr-crc

The effect of 5-aminolevulinic acid on canine peripheral blood mononuclear cells

Project description:The effect of 5-aminolevulinic acid on canine peripheral blood mononuclear cells

| PRJNA847171 | ENA