sod1 inhibitor  (MedChemExpress)

Journal: International Journal of Cardiology. Cardiovascular Risk and Prevention

Article Title: The sphingolipid metabolite sphingosine protects against hypertension by targeting metabolic-inflammatory crosstalk via the NLRP3 inflammasome

doi: 10.1016/j.ijcrp.2025.200562

Figure Lengend Snippet: SPH regulates NLRP3 inflammasome, ER stress, oxidative stress, and apoptosis/survival pathways in the hearts of hypertensive mice. (A, B) Representative Western blots and densitometric analysis for ER stress (GRP78), NLRP3 inflammasome components (NLRP3, ASC, C-Caspase-1, C-IL-1β, C-GSDMD), and oxidative stress (SOD1). (C–H) Relative mRNA expression of Nlrp3, Asc, Casp1, Gsdmd, IL1b, and IL18 by qRT-PCR. (I, J) Representative Western blots and densitometric analysis for apoptosis markers (BAX, BCL2, C-Caspase-3) and PI3K/AKT pathway proteins (p-PI3K, PI3K, p-AKT, AKT). GAPDH or total proteins were used for normalization. Data are mean ± SEM (n = 3 per group). Statistical analysis was by one-way ANOVA with Tukey's post-hoc test.

Article Snippet: The following primary antibodies were used: NLRP3 (Abcam, Cat# ab270449), ASC (Abcam, Cat#ab307560), Caspase-1 (Proteintech, Cat# 31020-1-AP), Cleaved Caspase-1 (CST, Cat# 89332), IL-1β(Abcam, Cat# ab254360), Cleaved IL-1β (CST, Cat#63124), IL- 18 (Proteintech, Cat# 33710-1-AP), SOD1 (Proteintech, Cat# 10269-1-AP), BCL2 (Proteintech, Cat# 26593-1-AP), BAX(Proteintech, Cat# 50599-2-Ig), and GRP78 (Proteintech, Cat# 11587-1-AP),GAPDH (Proteintech, Cat#60004-1-Ig), Phospho-PI3 Kinase p85 (CST, Cat#4228T), Phospho-AKT(Proteintech, Cat#66444-1-Ig), AKT(Proteintech, Cat#60203-2-Ig), GSDMD (N-Terminal) (Affinity,Cat# DF13758),GSDMD (Proteintech,Cat# 20770-1-AP).

Techniques: Western Blot, Expressing, Quantitative RT-PCR

Journal: International Journal of Cardiology. Cardiovascular Risk and Prevention

Article Title: The sphingolipid metabolite sphingosine protects against hypertension by targeting metabolic-inflammatory crosstalk via the NLRP3 inflammasome

doi: 10.1016/j.ijcrp.2025.200562

Figure Lengend Snippet: SPH protects human umbilical vein endothelial cells (HUVECs) from Angiotensin IIinduced injury, pyroptosis, and oxidative stress by inhibiting the NLRP3 inflammasome pathway. (A) Cell viability of HUVECs treated with AngII (1 μM) for 12 h followed by various concentrations of SPH (0.5–6 μM) for 24 h. (B) Cell viability of HUVECs treated with SPH alone for 24 h. (C, D) Representative Western blots and densitometric analysis for NLRP3 inflammasome components (NLRP3, ASC, c-Caspase-1, c-IL-1β), the pyroptosis effector N-GSDMD, ER stress marker GRP78, and oxidative stress marker SOD1. (E–J) Relative mRNA expression of NLRP3, ASC, CASP1, IL1B, IL18, and GSDMD by RT-qPCR. Data are the mean ± SEM of three independent experiments. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001, ∗∗∗∗P < 0.0001 vs. the AngII-only group, unless otherwise indicated.

Article Snippet: The following primary antibodies were used: NLRP3 (Abcam, Cat# ab270449), ASC (Abcam, Cat#ab307560), Caspase-1 (Proteintech, Cat# 31020-1-AP), Cleaved Caspase-1 (CST, Cat# 89332), IL-1β(Abcam, Cat# ab254360), Cleaved IL-1β (CST, Cat#63124), IL- 18 (Proteintech, Cat# 33710-1-AP), SOD1 (Proteintech, Cat# 10269-1-AP), BCL2 (Proteintech, Cat# 26593-1-AP), BAX(Proteintech, Cat# 50599-2-Ig), and GRP78 (Proteintech, Cat# 11587-1-AP),GAPDH (Proteintech, Cat#60004-1-Ig), Phospho-PI3 Kinase p85 (CST, Cat#4228T), Phospho-AKT(Proteintech, Cat#66444-1-Ig), AKT(Proteintech, Cat#60203-2-Ig), GSDMD (N-Terminal) (Affinity,Cat# DF13758),GSDMD (Proteintech,Cat# 20770-1-AP).

Techniques: Western Blot, Marker, Expressing, Quantitative RT-PCR

Journal: International Journal of Cardiology. Cardiovascular Risk and Prevention

Article Title: The sphingolipid metabolite sphingosine protects against hypertension by targeting metabolic-inflammatory crosstalk via the NLRP3 inflammasome

doi: 10.1016/j.ijcrp.2025.200562

Figure Lengend Snippet: SPH mitigates Angiotensin II-induced inflammasome activation, apoptosis, and oxidative stress in HUVECs. (A, B) Representative immunofluorescence images showing increased expression of NLRP3 (red, A) and ASC (green, B) in AngII-treated cells, which is reduced by subsequent SPH treatment. Scale bar = 100 μm. (C) TUNEL assay (green) demonstrating increased apoptosis in AngII-treated cells, which is attenuated by SPH. Scale bar = 100 μm. (D, E) Biochemical assays showing that SPH or MCC950 treatment reverses the AngII-induced decrease in SOD1 activity (G).NO (H) and increase in MDA levels (D). (F, G) DCFH-DA staining showing increased intracellular ROS (green) after AngII treatment, which is suppressed by SPH or MCC950. Representative images (F) and quantification (E) are shown. (I, J) ELISA results showing that SPH or MCC950 treatment inhibits the AngII-induced secretion of IL-1β (I) and IL-18 (J). (K) Scanning electron microscopy (SEM) images showing that SPH or MCC950 treatment improves the cell surface morphology and reduces features of pyroptotic damage induced by AngII. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Article Snippet: The following primary antibodies were used: NLRP3 (Abcam, Cat# ab270449), ASC (Abcam, Cat#ab307560), Caspase-1 (Proteintech, Cat# 31020-1-AP), Cleaved Caspase-1 (CST, Cat# 89332), IL-1β(Abcam, Cat# ab254360), Cleaved IL-1β (CST, Cat#63124), IL- 18 (Proteintech, Cat# 33710-1-AP), SOD1 (Proteintech, Cat# 10269-1-AP), BCL2 (Proteintech, Cat# 26593-1-AP), BAX(Proteintech, Cat# 50599-2-Ig), and GRP78 (Proteintech, Cat# 11587-1-AP),GAPDH (Proteintech, Cat#60004-1-Ig), Phospho-PI3 Kinase p85 (CST, Cat#4228T), Phospho-AKT(Proteintech, Cat#66444-1-Ig), AKT(Proteintech, Cat#60203-2-Ig), GSDMD (N-Terminal) (Affinity,Cat# DF13758),GSDMD (Proteintech,Cat# 20770-1-AP).

Techniques: Activation Assay, Immunofluorescence, Expressing, TUNEL Assay, Activity Assay, Staining, Enzyme-linked Immunosorbent Assay, Electron Microscopy

Journal: bioRxiv

Article Title: Sod1 trisomy causes ENS developmental defects and susceptibility to Hirschsprung disease via neuronal Ret suppression and glial remodeling

doi: 10.64898/2026.01.26.701837

Figure Lengend Snippet: (A) A schematic of the ∼23.8 kb human genomic fragment containing SOD1 and its regulatory elements (chr21:31,653,123-31,676,942; GRCh38) inserted into the mouse ROSA26 locus to generate the trisomic mouse line. (B) Quantitative RT-PCR demonstrating tissue-wide upregulation of Sod1/SOD1 gene expression in TS- Sod1/SOD1 neonates (P0) relative to wild-type (WT) littermates. Notably, expression in the forebrain reaches ∼1.7-fold, while distal colon, stomach, left and right kidneys and left and right ventricles of the heart show ∼1.5-fold elevation, consistent with trisomic dosage. (C) Gene expression analysis of the distal colon at P0 reveals significant dysregulation of Hirschsprung disease (HSCR)–associated genes in TS- Sod1/SOD1 mice. Expression of Ret , Ednrb , and Sema3c are significantly reduced, while Sema3a is upregulated ∼1.5-fold relative to WT controls. The results in (B) and (C) are mean ± SEM with p < 0.01 by two-way ANOVA with genotype and sex as factors.

Article Snippet: The diluted (1/5) total cDNA was subjected to Taqman gene expression (Thermo Fisher Scientific) using transcript-specific probes and primers for Sod1 (Mm01344233_g1; Thermo Fisher Scientific).

Techniques: Quantitative RT-PCR, Gene Expression, Expressing

Journal: bioRxiv

Article Title: Sod1 trisomy causes ENS developmental defects and susceptibility to Hirschsprung disease via neuronal Ret suppression and glial remodeling

doi: 10.64898/2026.01.26.701837

Figure Lengend Snippet: (A) UMAP of scRNA-seq data from the distal colon at P0 showing separation of WT and trisomic cells. (B) Cell-type annotation based on marker gene expression identifies five major ENS-derived populations: transcriptionally active progenitors, interneurons, inhibitory motor neurons, excitatory motor neurons, and glial cells. (C) Differentiation trajectory as inferred by Monocle shows glial cells as fully differentiated and distinct from neuronal lineages. Excitatory and inhibitory motor neurons occupy parallel pseudo-temporal branches, reflecting coordinated maturation. (D) Plot of relative cell type abundance across genotypes. All mature neuronal types and interneurons are reduced in TS- Sod1/SOD1 animals whereas transcriptionally active cells and glia are significantly increased. (E) Expression of Sod1/SOD1 across ENS cell types. All show elevated and at least 1.5-fold increased expression in cells from trisomic than disomic animals except for interneurons (∼1.2x). (F) The ratio of endogenous mouse Sod1 to human SOD1 transcripts is generally 2:1 as expected but glial cells exhibit a significantly higher ratio of 3.2. (G) Immunofluorescence quantification in distal colon sections stained for Tubb3 (neuronal marker) and Sod1 . TS- Sod1/SOD1 mice show ∼1.3-fold reduction in Tubb3 signals and ∼1.2-fold increase in Sod1 . Co-expressing cells ( Tubb3 and Sod 1) exhibit ∼1.25-fold lower intensity in TS- Sod1/SOD1 mice vs. WT. Data are shown as mean ± SEM; statistical significance (p < 0.01) was determined using two-way ANOVA or unpaired t-tests.

Article Snippet: The diluted (1/5) total cDNA was subjected to Taqman gene expression (Thermo Fisher Scientific) using transcript-specific probes and primers for Sod1 (Mm01344233_g1; Thermo Fisher Scientific).

Techniques: Marker, Gene Expression, Derivative Assay, Expressing, Immunofluorescence, Staining

Journal: bioRxiv

Article Title: Sod1 trisomy causes ENS developmental defects and susceptibility to Hirschsprung disease via neuronal Ret suppression and glial remodeling

doi: 10.64898/2026.01.26.701837

Figure Lengend Snippet: (A) Volcano plot of differential gene expression from scRNA-seq analysis of ENS cells in WT vs. TS- Sod1/SOD1 mice at P0 with1,878 significantly upregulated and 1,099 downregulated genes in trisomic mice. Upregulated genes include mouse homologs of human Chr21 genes such as Pcp4, Ndufv3, Prmt2, S100b, and Sod1 , while downregulated genes include the key neuronal markers Ret, Vip, Nos1, and Grin2b . (B) Heatmap of the gene expression of 10 genes from a core gene regulatory network associated with Hirschsprung disease. The ligands Gdnf and Edn3 (mesenchymal-specific) and transcription factors Gata2 and Nkx2-5 are not detected. Among expressed genes, Ret, Ednrb, Sox10 , and Rarb show reduced expression in trisomic ENS cells. (C) Cell-type–specific analysis of Ret expression reveals significant downregulation in excitatory motor neurons, inhibitory motor neurons, and transcriptionally active cells of TS- Sod1/SOD1 mice. Ret expression is mildly but significantly increased in interneurons but unchanged in glial cells. (D) Immunofluorescence quantification of RET protein in distal hindgut shows significantly reduced intensity in TS- Sod1/SOD1 as compared to WT mice, confirming reduced protein expression in vivo . Data are presented as mean ± SEM; statistical significance (p < 0.01) was determined by MAST GLM framework in Seurat or using t-tests where appropriate.

Article Snippet: The diluted (1/5) total cDNA was subjected to Taqman gene expression (Thermo Fisher Scientific) using transcript-specific probes and primers for Sod1 (Mm01344233_g1; Thermo Fisher Scientific).

Techniques: Gene Expression, Expressing, Immunofluorescence, In Vivo

Journal: bioRxiv

Article Title: Sod1 trisomy causes ENS developmental defects and susceptibility to Hirschsprung disease via neuronal Ret suppression and glial remodeling

doi: 10.64898/2026.01.26.701837

Figure Lengend Snippet: (A) Reclustering the glial cell population from scRNA-seq identifies its four distinct subtypes (microglia, astrocytes, active glia, and proliferating glia) based on differential gene expression. (B) Heatmap of the top marker genes for each glial subtype, including Plp1, S100b, Hmga2, Prdx1, Il1rapl1, Nfia, Camk1d, Mapk10 , etc., confirms subtype identity. (C) Average Sod1/SOD1 expression is elevated ∼1.6-fold in glial cells of TS- Sod1/SOD1 relative to WT mice. (D) Subtype-specific analysis showing ∼2-fold higher Sod1/SOD1 expression in proliferating and active glia, ∼1.5-fold in microglia, but no significant change in astrocytes. (E) Volcano plot showing differentially expressed genes in glial cells between genotypes. TS- Sod1/SOD1 glia shows 1,897 significantly upregulated and 844 downregulated genes. (F) Bar plot of glial subtype proportions reveals increased abundance of proliferating and active glia in the TS- Sod1/SOD1 ENS, and reduced proportions of astrocytes and microglia as compared to WT ENS. Data are presented as mean ± SEM; statistical significance (p < 0.01) was determined by MAST GLM framework in Seura t or two-way ANOVA.

Article Snippet: The diluted (1/5) total cDNA was subjected to Taqman gene expression (Thermo Fisher Scientific) using transcript-specific probes and primers for Sod1 (Mm01344233_g1; Thermo Fisher Scientific).

Techniques: Gene Expression, Marker, Expressing