Hao1 Is Not a Pathogenic Factor for Ectopic Ossifications but Functions to Regulate the TCA Cycle In Vivo

Kimura, Atsushi; Hirayama, Akiyoshi; Matsumoto, Tatsuaki; Sato, Yuiko; Kobayashi, Tami; Ikeda, Satsuki; Maruyama, Midori; Kaneko, Mari; Shigeta, Mayo; Ito, Eri; Soma, Tomoya; Miyamoto, Kana; Soga, Tomoyoshi; Tomita, Masaru; Oya, Akihito; Matsumoto, Morio; Nakamura, Masaya; Kanaji, Arihiko; Miyamoto, Takeshi

doi:10.3390/metabo12010082

Cited by 5 publications

(3 citation statements)

References 58 publications

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“…HAO1 is a peroxisomal enzyme that can regulate the tricarboxylic acid cycle. in oxidative stress [24,25]. EGR4 is involved in the regulation of learning, synaptic plasticity and memory dysfunction, and is implicated in the pathogenesis of schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Screening of potential biomarkers in propofol-induced neurotoxicity via bioinformatics prediction and experimental verification

2024

Am J Transl Res

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Objectives: To identify hub genes and biological processes of propofol-induced neurotoxicity and promote the development of pediatric anesthesiology. Methods: We downloaded the GSE106799 dataset from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened, then Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment analyses were performed on all DEGs. We identified potential ferroptosis genes in the pathogenesis of propofol-induced neurotoxicity. A key module was obtained after performing weighted gene co-expression network analysis (WGCNA) on the GSE106799 dataset. Hub genes were identified after the least absolute shrinkage and selection operator (LASSO) regression analysis of the intersection of DEGs and genes from the key module. We established a competing endogenous RNA network and predicted potential drugs according to the hub genes. Total RNA and proteins were extracted for real-time quantitative polymerase chain reaction and Western blotting, respectively. Results: A total of 112 DEGs, including 76 upregulated and 36 downregulated ones were screened out. Propofol-induced neurotoxicity involved processes such as nervous system development, activation of JAK/STAT and MAPK signaling pathways, vascular regeneration, and oxidative stress. The results of WGCNA suggested that the tan module was the most strongly associated with propofol-induced neurotoxicity. We identified 4 hub genes (EGR4, HAO1, ITK and GM14446) after LASSO regression analysis. Animal experiments demonstrated that propofol caused overexpression of the protein levels of HAO1, ITK and inflammatory factors in the brain, as well as the mRNA levels of HAO1, ITK and GM14446. Propofol inhibited expression of EGR4 at mRNA and protein levels. Conclusions: Previous studies have demonstrated that EGR4, HAO1, ITK and GM14446 play a role in intellectual development, neuroinflammation and neuronal differentiation. These hub genes may help us to find new preventive and therapeutic targets for propofol-induced neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

Screening of potential biomarkers in propofol-induced neurotoxicity via bioinformatics prediction and experimental verification

2024

Am J Transl Res

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“…Mainly expressed in the liver and pancreas, HAO1 is mostly active against the dicarbon substrate glycolate [28]. Additionally, recent studies have shown that HAO1 regulates TCA circulation [29], and targeted therapy of the HAO1 gene is expected to solve hyperoxaluria. HMGCLL1 is a highly homologous gene with HMGCL reported in the Genome Database in 2004.…”

Section: Discussionmentioning

confidence: 99%

Establishment and validation of a novel peroxisome-related genes prognostic risk model in Kidney Clear Cell Carcinoma

Zhao

Zhang

Huang

et al. 2023

Preprint

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Introduction: Kidney clear cell carcinoma is the most common subtype of renal cell carcinoma. Peroxisome play a role in the regulation of tumorigenesis and cancer progression. However, the prognostic value of peroxisome-related genes is rarely studied. The aim of this study was to establish a novel prognostic risk model for peroxisome-related genes in Kidney clear cell carcinoma. Materials and methods Based on TCGA data, we used univariate and multivariate Cox regression analyses to screen the differentially expressed genes initially, and LASSO Cox regression analysis was used to construct a prognostic risk model, which was verified with an internal validation cohort and a GSE22541 cohort. GO and KEGG analyses were performed to explore the differences in gene function and pathways between the high-risk and low-risk groups. The CIBERSORT database, ESTIMATE algorithm and TIMER database were used to calculate the immune cell infiltration scores of the samples and analyze immune cell infiltration. Results Thirty peroxisome-related genes were obtained by using differential analysis. We also screened 14 genes associated with the prognosis of KIRC patients by using univariate and multivariate Cox regression analyses. A nine-gene(ABCD1, ACAD11, ACAT1, AGXT, DAO, EPHX2, FNDC5, HAO1, andHNGCLL1) prognostic risk model was obtained via LASSO Cox regression analysis. GO and KEGG analyses showed that DEGs were mainly related to substance metabolism and transport and PPAR signaling pathways. Tumor immune infiltration results showed that the immune response in the high-risk group was suppressed, with higher tumor purity. The expression of nine genes was positively correlated with the level of immune cell infiltration. Conclusion Nine peroxisome-related genes may play an important role in KIRC tumor immunity. Combining the risk score with clinical factors, a nomogram was constructed. This nomogram can provide support for personalized treatment protocols for KIRC in the clinic.

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“…Hydroxyacid oxidase 1 (Hao1) was inactivated in mice, in the frame of its potential association with spinal canal stenosis, but no ectopic ossification was noticed [118].…”

Section: Other Peroxisomal Matrix Proteinsmentioning

confidence: 99%

Mouse Models to Study Peroxisomal Functions and Disorders: Overview, Caveats, and Recommendations

Kocherlakota¹,

Swinkels²,

Veldhoven³

et al. 2023

Methods in Molecular Biology

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During the last three decades many mouse lines were created or identified that are deficient in one or more peroxisomal functions. Different methodologies were applied to obtain global, hypomorph, cell type selective, inducible and knockin mice. Whereas some models closely mimic pathologies in patients, others strongly deviate or no human counterpart has been reported. Often, mice, apparently endowed with a stronger transcriptional adaptation, have to be challenged with dietary additions or restrictions in order to trigger phenotypic changes. Depending on the inactivated peroxisomal protein, several approaches can be taken to validate the loss-of-function. Here, an overview is given of the available mouse models and their most important characteristics.

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Hao1 Is Not a Pathogenic Factor for Ectopic Ossifications but Functions to Regulate the TCA Cycle In Vivo

Cited by 5 publications

References 58 publications

Screening of potential biomarkers in propofol-induced neurotoxicity via bioinformatics prediction and experimental verification

Screening of potential biomarkers in propofol-induced neurotoxicity via bioinformatics prediction and experimental verification

Establishment and validation of a novel peroxisome-related genes prognostic risk model in Kidney Clear Cell Carcinoma

Mouse Models to Study Peroxisomal Functions and Disorders: Overview, Caveats, and Recommendations

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