Journal: Toxicological sciences : an official journal of the Society of Toxicology

Article Title: Simvastatin Inhibits L-Type Ca2+-Channel Activity Through Impairment of Mitochondrial Function.

doi: 10.1093/toxsci/kfz068

Figure Lengend Snippet: Fig. 1. Simvastatin depolarizes the inner mitochondrial membrane potential, Δψmit. Representative traces of Rh123 fluorescence for primary mouse β-cells recorded in response to conditions indicated. Arrows show the

Article Snippet: Simvastatin and pravastatin were obtained from Tocris Bioscience (Bristol, UK).

Techniques: Membrane, Fluorescence

Journal: Toxicological sciences : an official journal of the Society of Toxicology

Article Title: Simvastatin Inhibits L-Type Ca2+-Channel Activity Through Impairment of Mitochondrial Function.

doi: 10.1093/toxsci/kfz068

Figure Lengend Snippet: Fig. 2. Simvastatin inhibits mitochondrial function in murine beta-cells. A) Effect of 0.1% vol/vol DMSO (n =

Article Snippet: Simvastatin and pravastatin were obtained from Tocris Bioscience (Bristol, UK).

Techniques:

Journal: Toxicological sciences : an official journal of the Society of Toxicology

Article Title: Simvastatin Inhibits L-Type Ca2+-Channel Activity Through Impairment of Mitochondrial Function.

doi: 10.1093/toxsci/kfz068

Figure Lengend Snippet: Figure 3. Glucose elicits calcium influx, which is inhibited by simvastatin. A) Representative intracellular calcium, [Ca2+]i, traces for five MIN6 beta-cells clusters all recorded in the same field in response to the

Article Snippet: Simvastatin and pravastatin were obtained from Tocris Bioscience (Bristol, UK).

Techniques:

Journal: Toxicological sciences : an official journal of the Society of Toxicology

Article Title: Simvastatin Inhibits L-Type Ca2+-Channel Activity Through Impairment of Mitochondrial Function.

doi: 10.1093/toxsci/kfz068

Figure Lengend Snippet: Figure 4. Simvastatin reverses the metabolic stimulation of L-type calcium channel activity. A-C) Single

Article Snippet: Simvastatin and pravastatin were obtained from Tocris Bioscience (Bristol, UK).

Techniques: Activity Assay

Journal: Nature Metabolism

Article Title: Fructose and glucose from sugary drinks enhance colorectal cancer metastasis via SORD

doi: 10.1038/s42255-025-01368-w

Figure Lengend Snippet: a , Sorbitol levels in CRC cells after 48 h of incubation under Glu + Fru (10 mM each) conditions, measured by LC–MS (DLD1, n = 5; HCT116, n = 6). b , Relative NAD⁺/NADH ratio in CRC cells after 48 h of incubation under Glu + Fru conditions, measured by LC–MS ( n = 3). c , Quantification of cytosolic Peredox NADH biosensor signals in WT and SORD KO CRC cells under Glu + Fru conditions after 24 h. The red/green fluorescence ratio reflects the NAD⁺/NADH ratio (DLD1 WT, n = 1205; DLD1 KO, n = 1147; HCT116 WT, n = 335; HCT116 KO, n = 311). Right, representative images; scale bars, 50 μm. d , Migration of SORD KO cells treated with vehicle (Veh) or α-ketobutyrate (α-KB) (DLD1, 1 mM; HCT116, 0.1 mM), assessed by transwell assay ( n = 3). Values were normalized to the Veh group. e , Migration of SORD KO cells expressing empty vector (Vec) or Lb NOX, assessed by transwell assay ( n = 3). Values were normalized to the Vec group. Left: schematic of the chemical reaction catalysed by Lb NOX. f , Schematic illustrating how SORD may enhance glycolysis under Glu + Fru conditions in CRC cells. The combination of glucose and fructose promotes regeneration of cytosolic NAD⁺, which is required to sustain high rates of aerobic glycolysis. g , LC–MS quantification of key glycolytic and TCA cycle metabolites in SORD WT and KO DLD1 cells after exposure to 10 mM U-[ 13 C]-glucose and 10 mM fructose in 10% dialysed FBS. Sampling times, 10 min for DHAP, GA3P, PEP and pyruvate; 3 h for acetyl-CoA, citrate and succinate; 12 h for malate ( n = 5). M+2 and M+3 indicate incorporation of two or three [ 13 C] carbon atoms, respectively. h , Heatmap of relative metabolite levels in sugar metabolism, glycolysis and the TCA cycle in SORD WT and KO DLD1 cells under Glu + Fru conditions, measured by LC–MS ( n = 6). Red indicates an increase; blue indicates a decrease. i , Metabolic pathways enriched in SORD WT versus KO cells (DLD1 and HCT116), based on RNA-seq data ( n = 4). Cells were incubated under Glu + Fru conditions for 48 h. Pathway analysis was performed using Qiagen Ingenuity Pathway Analysis on genes with P < 0.05 and |log 2 (fold change)| > 0.5. Blue bars indicate mevalonate-related pathways. The P value and fold change were calculated using Qiagen Ingenuity Pathway Analysis with Fisher’s exact test. j , Absolute quantities of key mevalonate pathway metabolites in SORD WT and KO DLD1 cells under Glu + Fru conditions, measured by LC–MS (WT, n = 3; KO, n = 4). k , Migration of SORD WT cells assessed by transwell assay under Glu + Fru conditions with vehicle or fluvastatin (Fluv) ( n = 3). Values were normalized to vehicle. DLD1, 1.5 μM; HCT116, 1 μM. l , Migration of SORD KO cells assessed by transwell assay with vehicle (or mevalonolactone (MVA; a cell-permeable form of mevalonate) ( n = 3). Values were normalized to vehicle. DLD1, 5 mM; HCT116, 2 mM. m , Liver metastatic tumour foci counts in mice that received vehicle ( n = 13) or simvastatin (Simv; n = 12) by daily oral gavage. Following caecal injection of HCT116 cells, athymic nude mice were treated with 100 μl day −1 of 10% DMSO (Veh) or 30 mg kg −1 day −1 simvastatin in 100 μl of 10% DMSO. All mice received 25% Glu + Fru (45:55) in drinking water for 5 weeks before liver metastasis assessment. n , Schematic showing how consumption of sugary drinks containing glucose and fructose may promote CRC migration and metastasis via SORD. All in vitro experiments were conducted under Glu + Fru (10 mM each) conditions unless otherwise specified. Data are presented as means and represent biological replicates; error bars, s.e.m. Statistical significance was determined by two-tailed unpaired Student’s t -test ( a – e and j – m ) or two-way ANOVA with Holm–Šídák post hoc test ( g ). **** P < 0.0001; *** P < 0.001; ** P < 0.01; * P < 0.05. Illustration in n created with BioRender.com . LDH, lactate dehydrogenase; DHAP, dihydroxyacetone phosphate; GA3P, glyceraldehyde-3-phosphate; 3PG, 3-phosphoglycerate; G3P, glycerol-3-phosphate; PEP, phosphoenolpyruvate; OAA, oxaloacetate; HMG-CoA, 3-hydroxy-3-methylglutaryl-CoA; MVA-5P, mevalonate-5-phosphate; MVA-5PP, mevalonate-3,5-bisphosphate; IPPP, isopentenyl pyrophosphate; GPP, geranyl pyrophosphate.

Article Snippet: In the simvastatin treatment experiment, mice were treated with 30 mg kg −1 day −1 simvastatin (Selleckchem, S1792) in PBS containing 10% DMSO by oral gavage.

Techniques: Incubation, Liquid Chromatography with Mass Spectroscopy, Fluorescence, Migration, Transwell Assay, Expressing, Plasmid Preparation, Sampling, RNA Sequencing, Injection, In Vitro, Two Tailed Test

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Limb girdle muscular disease caused by HMGCR mutation and statin myopathy treatable with mevalonolactone.

doi: 10.1073/pnas.2217831120

Figure Lengend Snippet: Fig. 5. Oral mevalonolactone treatment in murine statin-induced myopathy. Mice were treated daily with intraperitoneal injections of either Cerivastatin, Simvastatin, or 0.9% saline solution for 14 d, with or without 200 mg/kg oral mevalonolactone. n = 4 in each group. Mice were housed in PhenoMaster cages for the last 3 d of treatment. (A) Grip strength test on day 14. (B) Hanging wire test on day 14. (C) Hanging wire test throughout the study. (D–I) Measurements of strength and endurance from PhenoMaster cages. (J–K) H&E stained diaphragm muscles of a subject from the Cerivastatin group (J) and the Cerivastatin + mevalonolactone group (K). No signs of fibrosis, necrosis, or inflammation were evident. Diaphragm, gastrocnemius, and quadriceps muscles were examined from two subjects in every group. Statistical analysis using one-way ANOVA with multiple comparisons.

Article Snippet: Simvastatin, alkaline hydrolyzed (47) (sc-200829, Santa Cruz biotechnology) 20 mg/kg/d IP with/without 200 mg/kg/d mevalonolactone in drinking water.

Techniques: Saline, Staining, Muscles

Journal: Journal of molecular and cellular cardiology

Article Title: MitoPlex: A Targeted Multiple Reaction Monitoring Assay for Quantification of a Curated Set of Mitochondrial Proteins

doi: 10.1016/j.yjmcc.2020.03.011

Figure Lengend Snippet: (A) Protein abundance heatmap for all MitoPlex proteins detected in organs of mice treated for 10 days with either DMSO or 20 mg/kg simvastatin. Expression is displayed as row z-score, ranging from undetected / below lower limit of quantification (white) to highest in the dataset (dark orange). (B) Log2-fold changes in mitochondrial proteins in the tissues of simvastatin-treated mice (vs. vehicle) as reported by MitoPlex; values are means ±SD (n=4), unpaired t-test, *p<0.05. (C) Log2-fold changes in mitochondrial proteins and metabolites of the TCA cycle in the tissues of mice treated with simvastatin (vs. vehicle). Proteins are labeled in red and metabolites in blue.

Article Snippet: Mouse Simvastatin Treatment Eight sixteen-week old C57/BL6 mice were injected with either vehicle (DMSO) or 20mg/kg of simvastatin (Toronto Research Chemicals, S485000) once a day intraperitoneally for 10 days [ 61 , 62 ].

Techniques: Expressing, Labeling

Journal: Journal of molecular and cellular cardiology

Article Title: MitoPlex: A Targeted Multiple Reaction Monitoring Assay for Quantification of a Curated Set of Mitochondrial Proteins

doi: 10.1016/j.yjmcc.2020.03.011

Figure Lengend Snippet: (A) Phase contrast microcopy images representative of C2C12 myotubes 6 days post differentiation in the presence of DMSO, 2uM simvastatin, 5uM CoQ1, or both. (B) Respirometry trace and respiratory rates from C2C12 myotubes differentiated in the presence DMSO, 2uM simvastatin, 5uM CoQ1, or both. One-way analysis of variance (ANOVA) vs DMSO, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 are means ±SD, n=3. (C) Immunoblot analysis of whole cell lysates with the OXPHOS antibody cocktail and quantification of the results, normalized to Ponceau staining. One-way analysis of variance (ANOVA) vs DMSO, *p<0.05, **p< 0.01, ***p<0.001, ****p<0.0001; representative immunoblot is shown, values are means ±SD, n=3). (D) Protein abundance heatmap for all MitoPlex proteins detected in C2C12 myotubes differentiated in the presence DMSO, 2uM simvastatin, 5uM CoQ1, or both. Expression is displayed as row z-score, ranging from undetected / below lower limit of quantification (white) to highest in the dataset (dark orange). (E) Comparison of Log2-fold changes in mitochondrial proteins as reported by MitoPlex; values are means ±SD (n=3), unpaired t-test, *p<0.05 **p<0.01. (F) Heat map analysis of LC-MS metabolomics of samples from (D).

Article Snippet: Mouse Simvastatin Treatment Eight sixteen-week old C57/BL6 mice were injected with either vehicle (DMSO) or 20mg/kg of simvastatin (Toronto Research Chemicals, S485000) once a day intraperitoneally for 10 days [ 61 , 62 ].

Techniques: Western Blot, Staining, Expressing, Liquid Chromatography with Mass Spectroscopy

Journal: Journal of molecular and cellular cardiology

Article Title: MitoPlex: A Targeted Multiple Reaction Monitoring Assay for Quantification of a Curated Set of Mitochondrial Proteins

doi: 10.1016/j.yjmcc.2020.03.011

Figure Lengend Snippet: Log2-fold changes in mitochondrial proteins and metabolites of the TCA cycle in the tissues of mice treated with simvastatin (vs. vehicle). Proteins are labeled in red and metabolites in blue.

Article Snippet: Mouse Simvastatin Treatment Eight sixteen-week old C57/BL6 mice were injected with either vehicle (DMSO) or 20mg/kg of simvastatin (Toronto Research Chemicals, S485000) once a day intraperitoneally for 10 days [ 61 , 62 ].

Techniques: Labeling