Gene Expression Changes in a Model Neuron Cell Line Exposed to Autoantibodies from Patients with Traumatic Brain Injury and/or Type 2 Diabetes

Zimering, Mark B; Delic, Vedad; Citron, Bruce A.

doi:10.1007/s12035-021-02428-4

Cited by 3 publications

(2 citation statements)

References 34 publications

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“…The ZFAND2B gene encodes a protein containing an AN1-type zinc finger and a ubiquitin interaction motif and regulates the insulin-like growth factor receptor signaling pathway [50]. The significant missense mutation (rs109446852) that accounts for about 2% of genetic variance results in a single amino acid substitution that does not affect protein function or structure.…”

Section: Discussionmentioning

confidence: 99%

Identification of Missense Variants Affecting Carcass Traits for Hanwoo Precision Breeding

Lee,

Kim,

Dinh

et al. 2023

Genes

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This study aimed to identify causal variants associated with important carcass traits such as weight and meat quality in Hanwoo cattle. We analyzed missense mutations extracted from imputed sequence data (ARS-UCD1.2) and performed an exon-specific association test on the carcass traits of 16,970 commercial Hanwoo. We found 33, 2, 1, and 3 significant SNPs associated with carcass weight (CW), backfat thickness (BFT), eye muscle area (EMA), and marbling score (MS), respectively. In CW and EMA, the most significant missense SNP was identified at 19,524,263 on BTA14 and involved the PRKDC. A missense SNP in the ZFAND2B, located at 107,160,304 on BTA2 was identified as being involved in BFT. For MS, missense SNP in the ACVR2B gene, located at 11,849,704 in BTA22 was identified as the most significant marker. The contribution of the most significant missense SNPs to genetic variance was confirmed to be 8.47%, 2.08%, 1.73%, and 1.19% in CW, BFT, EMA, and MS, respectively. We generated favorable and unfavorable haplotype combinations based on the significant SNPs for CW. Significant differences in GEBV (Genomic Estimated Breeding Values) were observed between groups with each favorable and unfavorable haplotype combination. In particular, the missense SNPs in PRKDC, MRPL9, and ANKFN1 appear to significantly affect the protein’s function and structure, making them strong candidates as causal mutations. These missense SNPs have the potential to serve as valuable markers for improving carcass traits in Hanwoo commercial farms.

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Section: Discussionmentioning

confidence: 99%

Identification of Missense Variants Affecting Carcass Traits for Hanwoo Precision Breeding

Lee,

Kim,

Dinh

et al. 2023

Genes

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“…The mechanism of action of Sertuercept is not known, but it may differ from other 5-HT2A receptor antagonists. In a recent report, brief exposure of neuroblastoma cells to active, human diabetic 5-HT2AR targeting autoantibodies resulted in significant downregulation of mRNA expression in the G protein-coupled receptor kinase 3 gene (GRK3) [31]. G-protein receptor kinases are a family of serine-threonine kinases which are activated by certain ligand occupied G-protein coupled receptors causing phosphorylation of the GPCR and directing arrestin-mediated receptor desensitization [8].…”

Section: Discussionmentioning

confidence: 99%

A Serotonin 2A-Receptor Decoy Peptide Potently Lowers Blood Pressure in Male Zucker Diabetic, Fatty, Hypertensive Rats

Zimering

2021

Endocrinol Diabetes Metab J

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Aims: To test whether a novel 5-hydroxytryptamine 2A decoy receptor peptide, SN..8 (Sertuercept), administered via intraperitoneal injection, acutely lowers arterial blood pressure in obese, hypertensive male Zucker diabetic rats (ZDF). To examine the safety, tolerability and possible reno-protective effects following chronic alternate daily administration of Sertuercept (for 10 weeks) in the male ZDF rat.Methods: Systolic and diastolic blood pressure were determined at baseline and regular intervals for up to 48 hours after a single IP administration of either Sertuercept (2 mg/kg), vehicle (saline) or an identical concentration of a scrambled sequence of the decoy receptor peptide, LN…8, in male ZDF and Zucker lean rats using tail cuff plethysmography. Plasma autoantibodies were obtained in thirteen male ZDF rats for determination of 5-hydroxytryptamine 2A receptor-mediated neurotoxicity using an acute neurite retraction assay in mouse neuroblastoma cells. Rats were sacrificed at 25-weeks of age, the kidneys were perfused, fixed and sections were stained using Masson's trichrome for semi-quantitative determination of glomerular and interstitial fibrosis.Results: Sertuercept (2 mg/kg IP) potently lowered systolic and diastolic blood pressure in both 11-week-old and 25-week-old male ZDF rats and in a subset of hypertensive Zucker lean rats. There was no significant blood pressure-lowering effect of vehicle (saline) or scrambled peptide sequence (LN.8). Blood pressure-lowering was rapid in onset (15-30 minutes following IP injection) and sustained for at least 24 hours. Alternate daily IP administration of 2 mg/kg dose of Sertuercept vs. scrambled peptide (for 10 weeks) was safe, well-tolerated and associated with a significant decrease in glomerulosclerosis in 25-week-old male ZDF rats. Plasma autoantibody-induced neurotoxicity correlated significantly with the global index of renal fibrosis severity in 25-week-old male ZDF rats.Conclusions: These data indicate potent arterial blood pressure-lowering efficacy from a decoy receptor peptide comprised of a second extracellular loop region of the human 5-hydroxytryptamine receptor. Chronic administration of the decoy receptor peptide (10 weeks) was safe, well-tolerated and protected against renal glomerulosclerosis in the male ZDF rat.

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Integrative system biology and mathematical modeling of genetic networks identifies shared biomarkers for obesity and diabetes

Bima¹,

Elsamanoudy²,

Albaqami³

et al. 2022

MBE

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<abstract> <p>Obesity and type 2 and diabetes mellitus (T2D) are two dual epidemics whose shared genetic pathological mechanisms are still far from being fully understood. Therefore, this study is aimed at discovering key genes, molecular mechanisms, and new drug targets for obesity and T2D by analyzing the genome wide gene expression data with different computational biology approaches. In this study, the RNA-sequencing data of isolated primary human adipocytes from individuals who are lean, obese, and T2D was analyzed by an integrated framework consisting of gene expression, protein interaction network (PIN), tissue specificity, and druggability approaches. Our findings show a total of 1932 unique differentially expressed genes (DEGs) across the diabetes versus obese group comparison (p≤0.05). The PIN analysis of these 1932 DEGs identified 190 high centrality network (HCN) genes, which were annotated against 3367 GO terms and functional pathways, like response to insulin signaling, phosphorylation, lipid metabolism, glucose metabolism, etc. (p≤0.05). By applying additional PIN and topological parameters to 190 HCN genes, we further mapped 25 high confidence genes, functionally connected with diabetes and obesity traits. Interestingly, <italic>ERBB2, FN1, FYN, HSPA1A, HBA1</italic>, and <italic>ITGB1</italic> genes were found to be tractable by small chemicals, antibodies, and/or enzyme molecules. In conclusion, our study highlights the potential of computational biology methods in correlating expression data to topological parameters, functional relationships, and druggability characteristics of the candidate genes involved in complex metabolic disorders with a common etiological basis.</p> </abstract>

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Gene Expression Changes in a Model Neuron Cell Line Exposed to Autoantibodies from Patients with Traumatic Brain Injury and/or Type 2 Diabetes

Cited by 3 publications

References 34 publications

Identification of Missense Variants Affecting Carcass Traits for Hanwoo Precision Breeding

Identification of Missense Variants Affecting Carcass Traits for Hanwoo Precision Breeding

A Serotonin 2A-Receptor Decoy Peptide Potently Lowers Blood Pressure in Male Zucker Diabetic, Fatty, Hypertensive Rats

Integrative system biology and mathematical modeling of genetic networks identifies shared biomarkers for obesity and diabetes

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