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

ABSTRACT: 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.

ORGANISM(S): Arabidopsis thaliana

PROVIDER: GSE27704 | GEO | 2011/04/01

SECONDARY ACCESSION(S): PRJNA138123

REPOSITORIES: GEO

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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

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

Project description:5-aminolevulinic acid (ALA) is one of the natural amino acids and a product of the first heme synthesis pathway in mitochondria. Recently, a supplement containing ALA is available in Japan and used for the purpose of the enhancement of ATP synthesis via mitochondrial activity. In humans, the immunomodulatory effect of ALA has attracted attention as a new function of ALA, and its application to cancer, inflammatory disease, and autoimmune diseases are being investigated. In the present study, to evaluate the effects of ALA on canine immunity, we performed in vitro studies using peripheral blood mononuclear cells (PBMC) from healthy dogs. Heme oxygenase-1 protein was expressed in Madin-Darby Canine Kidney cells and PBMCs treated with 5-ALA and ferrous sodium citrate (SFC), which showed that ALA works in dogs as well as humans. When PBMCs were stimulated with concanavalin A (ConA), the addition of ALA resulted in a significant increase in interferon-gamma (IFN-γ) produced by ConA-stimulated PBMCs. A comprehensive genetic alteration using next-generation RNA sequences (RNA-seq) was performed. From the result of RNA-seq, ALA enhanced the gene expression of T cell immunity including Th1, Th2, and Th17 subsets. In particular, the IL-17 signaling pathway was significantly upregulated. Then, we confirmed that ALA promoted the production of interleukin (IL)-17A in ConA-stimulated PBMCs. Together, these findings reveal that ALA promotes heme synthesis in mitochondria and enhances ConA-induced T cell immune responses in canine PBMCs.

2022-08-05 | GSE205679 | 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

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

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

Sodium ferrous citrate and 5-aminolevulinic acid improve type 2 diabetes by maintaining muscle and mitochondrial health

Project description:Objective Improving mitochondrial function is a promising strategy for intervention in type 2 diabetes mellitus. This study investigated the preventive effects of sodium ferrous citrate (SFC) and 5-aminolevulinic acid phosphate (ALA) on several metabolic dysfunctions associated with obesity because they have been shown to alleviate abnormal glucose metabolism in humans. Methods Six-week-old male C57BL/6J mice were fed with a normal diet, a high-fat diet, or a high-fat diet supplemented with SFC and ALA for 15 weeks. Results The simultaneous supplementation of SFC + ALA to high-fat diet-fed mice prevented loss of muscle mass, improved muscle strength, and reduced obesity and insulin resistance. SFC + ALA prevented abnormalities in mitochondrial morphology and reverted the diet effect on the skeletal muscle transcriptome, including the expression of glucose uptake and mitochondrial oxidative phosphorylation-related genes. In addition, SFC + ALA prevented the decline in mitochondrial DNA copy number by enhancing mitochondrial DNA maintenance and antioxidant transcription activity, both of which are impaired in high-fat diet-fed mice during long-term fasting. Conclusions These findings suggest that SFC + ALA supplementation exerts its preventive effects in type 2 diabetes mellitus via improved skeletal muscle and mitochondrial health, further validating its application as a promising strategy for the prevention of obesity-induced metabolic disorders.

2023-02-23 | GSE201092 | GEO

Transcriptomic analysis of mouse brain tissue treated by 5-ALA-mediated photodynamic therapy

Project description:We report the application of 5-ALA ( 5-Aminolevulinic acid)-mediated photodynamic therapy on mouse brain tissue, and further explored the impact of PDT on nervous system.

2021-04-30 | GSE173615 | GEO

Transcriptomic analysis of mouse brain tissue post treatment by 5-ALA-mediated photodynamic therapy at different timepoints

Project description:We report the application of 5-ALA ( 5-Aminolevulinic acid)-mediated photodynamic therapy on mouse brain tissue, and further explored the impact of PDT on nervous system.

2022-04-22 | GSE200906 | GEO

SCOPE-seq Analysis of Intra-operative Labeling Specificity of 5-ALA for Glioblastoma

Project description:Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor, and surgical resection is a key part of the standard-of-care. In fluorescence-guided surgery (FGS), fluorophores are used to differentiate tumor tissue from surrounding normal brain. The heme synthesis pathway converts 5-aminolevulinic acid (5-ALA), a fluorogenic substrate, to the fluorophore protoporphyrin IX (PpIX). The resulting fluorescence is thought to be specific to transformed glioma cells, but this specificity has not been examined at single cell level. Here, we performed paired single cell imaging and RNA sequencing of individual cells (SCOPE-seq2) on human GBM surgical specimens with visible PpIX fluorescence from patients who received 5-ALA prior to surgery. SCOPE-seq2 allows us to simultaneously measure PpIX fluorescence by imaging and unambiguously identify transformed glioma cells from single-cell RNA-seq (scRNA-seq). We observed that 5-ALA treatment results in labeling that is not specific to transformed tumor cells. In cell culture experiments, we further demonstrated untransformed cells can be labeled by 5-ALA directly or by PpIX secreted from surrounding transformed cells. In acute slice cultures from mouse glioma models, we showed that 5-ALA preferably labels GBM tumor tissue over non-neoplastic brain tissue at bulk level, and that this contrast is not due to blood-brain-barrier disruption. Taken together, our findings support the use of 5-ALA as an indicator of GBM tissue, but not as a specific marker of transformed glioma cells.

2022-11-30 | GSE218331 | GEO

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