Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Elevated MG-H1 in glo1-/-aldh3a1-/- zebrafish caused microvasculature alterations and glucose metabolism impairment via decreased proteasome activity

ABSTRACT: Dicarbonyl stress is characterized by the abnormal accumulation of dicarbonyl reactive metabolites, leading to increased modification of proteins, DNA and lipids, thereby contributing to cellular and tissue dysfunction in diabetes, diabetic complications and other diseases. glo1 knockout zebrafish exhibited moderately increased MG levels, yet this was inadequate to induce trunk vessels alterations due to elevated ALDH activity and mRNA expression levels, which partially act as compensatory mechanism. Excess 4-HNE induced pancreas dysfunction in aldh3a1 knockout zebrafish larvae, inhibiting insulin expression and thereby facilitating hyperglycemia and hyaloid vasculature alterations. To evaluate the combined function of Glo1 and Aldh3a1 in glucose homeostasis and diabetic microvasculature, glo1-/-aldh3a1-/- zebrafish were generated using CRISPR/Cas9 technology. Multiple experiments are performed regarding vasculature alterations, glucose homeostasis, transcriptome, and metabolomics in Tg(fli1:EGFP) zebrafish. glo1-/-aldh3a1-/- zebrafish larvae displayed angiogenic hyaloid vasculature caused by the elevated MG-H1 and decreased proteasomal chymotrypsin-like activity, which could be rescued by the MG-H1 scavenger L-carnosine and proteasome activator Betulinic acid treatments. In adult glo1-/-aldh3a1-/- zebrafish, impaired glucose metabolism, angiogenic retina vasculature and thickened GBM were observed. Thus, our data suggested that an important upstream factor contributing to these phenomena in the context of lacking glo1 and aldh3a1 is MG-H1, possibly through reduced proteasome activity.

ORGANISM(S): Danio rerio

PROVIDER: GSE270442 | GEO | 2024/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Elevated MG-H1 in glo1-/-aldh3a1-/- zebrafish caused microvasculature alterations and glucose metabolism impairment via decreased proteasome activity

Project description:Elevated MG-H1 in glo1-/-aldh3a1-/- zebrafish caused microvasculature alterations and glucose metabolism impairment via decreased proteasome activity

| PRJNA1126644 | ENA

The function and mechanism of aldh9a1b in diabetes

Project description:Reactive aldehydes such as 4-HNE, MDA and acrolein are implicated in the pathological development of diabetes as their widespread and universally exposed characteristics. Trans, trans-2,4-decadienal (tt-DDE) come from lipid peroxidation of omega-6 and is most abundant aldehyde in cooking oil fumes, while, its role in diabetes remained unknown. Aldh9a1 is a cytosolic enzyme that catalyze the NAD+-dependent oxidation of a variety of aldehydes and has its homology aldh9a1b in zebrafish. To investigate the function of endogenous and exogenous tt-DDE, aldh9a1b knockout zebrafish are established using CRISPR/Cas9 technology. TT-DDE was confirmed to act as substrate for aldh9a1b and a series of experiments are performed on a histological, metabolomic and transcriptomic level in aldh9a1b-/- zebrafish. Both aldh9a1b-/- larvae and adult fish displayed abnormal retinal vasculature and impaired glucose homeostasis, which are caused by tt-DDE induced downregulated insulin signaling pathway. Furthermore, the abnormal hyaloid vasculature in the fish can be reversed by insulin receptor sensitizer and metformin exhibited strongest effects among them. Altogether, these results identified tt-DDE as the preferred substrate for aldh9a1b, which subsequently causes microvascular damage and impaired glucose metabolism by insulin resistance.

2023-12-08 | GSE223340 | GEO

Impairment of methylglyoxal detoxification systems causes mitochondrial dysfunction and behavioral deficits

Project description:Methylglyoxal (MG) is a reactive alpha-dicarbonyl by-product of glycolysis. Several bio-defense systems to detoxify the highly toxic MG are equipped in our body, including an enzymatic system by glyoxalase (GLO) 1 and GLO2 and a scavenge system by vitamin B6 (VB6). We have reported that some population of patients with schizophrenia shows impairment of the MG detoxification systems. Although we have evidences showing a link between impairment of MG detoxification systems and development of schizophrenia, the molecular mechanism to connect them remains poorly understood. Here, we generated a novel mouse model for MG detoxification deficits by feeding Glo1 knockout mice with VB6-lacking diets (KO/VB6(-)), and evaluate effects of impaired MG detoxification systems on brain function. KO/VB6(-) mice showed the accumulation of MG in the prefrontal cortex (PFC), hippocampus, and striatum, and displayed schizophrenia-like behavioral deficits, such as social deficits, cognitive impairment, a sensorimotor deficit in the prepulse inhibition test. Furthermore, we found aberrant gene expression related to mitochondria function in the PFC of the KO/VB6(-) mice by RNA-seq and weighted gene correlation network analysis (WGCNA). Finally, we actually demonstrated respiratory deficits in mitochondria isolated from the PFC of KO/VB6(-) mice. These findings suggest that MG detoxification deficits might cause schizophrenia-like behavioral deficits via mitochondrial dysfunction in the PFC.

2021-07-20 | GSE149585 | GEO

Hepatic dysregulation of glyoxalase 1 in preclinical models and patients with non-alcoholic fatty liver disease

Project description:Background & Aims: Although non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, aspects of its molecular pathogenesis are unknown and clinical biomarkers for early diagnosis and accurate disease staging remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of NAFLD and explore the utility of novel candidate biomarkers in NAFLD patients. Methods: Liver protein fractions were analyzed in a relative quantitative proteomic approach utilizing isobaric tags for relative and absolute quantitation (iTRAQ) labeling combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential expression was confirmed independently by western blotting and immunohistochemistry, first in mouse sections and then in biopsies from paediatric NAFLD patients. Candidate serum biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results: Through proteomic profiling we identified decreased expression of hepatic glyoxalase 1 (GLO1) in an animal model of NAFLD. GLO1 protein levels were also found reduced in tissue biopsies from pediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid-loading in hepatocytes, GLO1 is first hyper-acetylated then ubiquitinylated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 62 biopsy-confirmed adult NAFLD patients serum levels of the primary methylglyoxal-derived advanced glycated endproduct, hydroimidazolone (MG-H1) were found strongly correlated with body mass index (r=0.619, p<0.0001). Conclusions: We characterize, for the first time, the post-translational modification and regulation of GLO1 expression in response to hepatic lipid loading with functional consequences in NAFLD patients.

2018-02-16 | PXD001442 | Pride

Next Generation Sequencing Facilitates Quantitative Analysis of Wildtype and aldh3a1-/- Zebrafish Embryo Transcriptomes

Project description:Our previous experiments showed the function of Aldh3a1 was related to pancreas and insulin secretion and knockout of Aldh3a1 led to destoryed pancreas. To understand how the impaired pancreas reflects at the transcriptome level, we performed full genome RNA-Seq between aldh3a1+/+ and aldh3a1-/- larvae at 48 hpf.An overview of RNA-Seq, including quality control, principal component analysis (PCA), volcano plots of regulated genes and Top 20 KEGG pathway analysis showed comparable properties between aldh3a1 mutants and wild type. We found the insulin signalling pathway was reduced significantly via gene set enrichment analysis (normalized enrichment score, -1.72; p=0.0006). Interestingly, endocrine pancreas but not exocrine pancreas development pathway was significantly down-regulated in aldh3a1 mutants . Taken together, these results further suggest Aldh3a1 as an important regulator in the development, morphology and insulin secretion function of primary pancreas. Furthermore, we offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within zebrafish larvae. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.

2020-10-06 | GSE151770 | GEO

activated sludge metagenome

Project description:H1-AK-MG Metagenome

| PRJNA261475 | ENA

Proteomic response to cytotoxicity of methylglyoxall

Project description:Tumor glycolysis is a target for cancer chemotherapy. Methylglyoxal (MG) is a reactive metabolite formed mainly as a by-product in anaerobic glycolysis, metabolized by glyoxalase 1 (Glo1) of the glyoxalase system. MG is increased to cytotoxic levels by clinical anticancer drugs, contributing to their mechanism of action. We investigated the role of the proteomic response to MG in mediating cytotoxicity. The proteomic response to MG-induced cytotoxicity was explored by high mass resolution proteomics of cytoplasmic and other subcellular protein extracts. MG induced decrease of mitochondrial and spliceosomal proteins. Spliceosomal proteins were targets of MG modification. We conclude that MG-mediated cytotoxicity targets the spliceosome.

2021-11-02 | PXD029315 | Pride

Expression data from BAC transgenic mice overexpressing Glo1

Project description:We generated mice with a transgenic BAC on a B6 background. The BAC contains Glo1, and the transgenic mice were found to overexpress Glo1. We performed a microarray on whole-brain RNA of adult mice to identify differentially expressed genes resulting from Glo1 overexpression. Wild type (WT) and transgenic (Tg) littermates were used. Mice were adult males, and RNA was extracted from whole brains.

2012-03-26 | E-GEOD-36819 | biostudies-arrayexpress

Alx function in the developing eye

Project description:Zebrafish with loss-of-function alx1 mutations develop with craniofacial and ocular defects of variable penetrance, likely due to compensatory upregulation in expression of a paralogous gene, alx3. We show that zebrafish alx1; alx3 mutants develop with highly penetrant cranial and ocular defects that resemble human ALX1-linked FND. alx1 and alx3 are expressed in anterior cranial neural crest (aCNC), which gives rise to the anterior neurocranium (ANC), anterior segment structures of the eye and vascular pericytes. Consistent with a functional requirement for alx genes in aCNC, alx1; alx3 mutants develop with nearly absent ANC and grossly aberrant hyaloid vasculature and ocular anterior segment, but normal retina. In vivo lineage labeling identified a requirement for alx1 and alx3 during aCNC migration, and transcriptomic analysis suggested oxidative stress response as a key target mechanism of this function. Oxidative stress is a hallmark of fetal alcohol toxicity, and we found increased penetrance of facial and ocular malformations in alx1 mutants exposed to ethanol, consistent with a protective role for alx1 against ethanol toxicity.

2022-05-07 | GSE202238 | GEO

Single-Cell Characterization of the Frizzled 5 (Fz5) Mutant Mouse and Human Persistent Fetal Vasculature (PFV)

Project description:During early development, a transitory fetal vasculature of the vitreous hyaloid vessels (HV) provides temporary nutrients for the developing lens and retina. HV regresses when the intraretinal vasculature develops to replace its function. Failure in regression of the HV leads to persistent fetal vasculature (PFV), a pathological condition accounting for 4.8% children blindness in the USA. To date, the HV formation and regression as well as the related PFV pathogenesis are largely unknown. In this study, by single-cell RNA sequencing (scRNA-seq) the vitreous cells derived from normal and the Fzd5 mutant mice at two time points, postnatal day 3 (P3) and P6, we collectively defined 10 major cell types, present in both wild type and mutant developing vitreous but with much higher numbers of endothelial cells, macrophages, erythroid-like cells, pericytes, smooth muscle cells, fibroblasts and melanocytes in the P3 mutants. Both mutant and wild type cell types declined to similar sizes at P6 with varied compositions of sub clusters. We further compared gene expression profiles of residual major sub clusters at P6, and showed altered metabolic activities of the mutant cells. Additionally, two macrophage clusters expressed markers for hyalocytes supporting the notion that these cells are of macrophage origin. The melanocytes predominantly existed in the Fzd5 mutants expressing neural crest markers including Pax3 and Sox10, similar to that of choroidal pigment cells. Taken together, these data revealed cell features of normal and pathological hyaloid tissues, which has not been known precedentially.

2023-05-31 | GSE203116 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data