Dataset Information

Mitochondrial activity disruption and local muscle damage induced in mice by Scolopendra polymorpha venom.

ABSTRACT: Background:Scolopendra polymorpha (S. polymorpha) is a predatory centipede whose venom contains a multiplicity of biochemical effectors that can cause muscle damage and cumulative cell destruction in its prey. Despite previous investigations of S. polymorpha and other centipede venoms, there is a lack of information on the morphological and biochemical patterns elicited by their myotoxic effects. To elucidate these processes, this paper presents evidence of skeletal muscle damage, and alterations in key biochemical mediators that appear only after exposure to centipede venom. Methods:Venom was collected and fractionated using RP-HPLC; mouse extensor digitorum longus (EDL) muscle was exposed to whole venom and venom fractions to evaluate myotoxicity by means of creatine kinase (CK) - a muscle damage marker - activity measurements and histochemical analysis. Results:CK activity was higher in EDL muscle exposed to venom than in unexposed muscle. This increase was observed after 15 min of venom incubation, and remained stable up to 45 min. Venom-exposed EDL muscle showed signs of muscle damage including necrosis, loss of fascicular structure as well as mitochondrial accumulations and ragged red fibers (RRF), suggesting an impairment in the normal mitochondrial arrangement. Nicotinamide adenine dinucleotide (NADH) and cytochrome oxidase (COX) tests also indicate that respiratory complexes might be affected. Conclusion:Our results suggest a different biochemical composition of S. polymorpha venom, based on the different effects of four venom fractions on the cells tested, according to statistical evidence. Fractions F6 and F7 caused the most important alterations.

SUBMITTER: Robles JT

PROVIDER: S-EPMC7269145 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mitochondrial activity disruption and local muscle damage induced in mice by <i>Scolopendra polymorpha</i> venom.

Robles Judith Tabullo De JT Valverde Francisca Fernández FF Cisneros Lucero Valladares LV Villeda Juana Hernández JH Sánchez-Reyes Ayixon A Gutiérrez María Del Carmen MDC

The journal of venomous animals and toxins including tropical diseases 20200529

<h4>Background</h4><i>Scolopendra polymorpha (S. polymorpha)</i> is a predatory centipede whose venom contains a multiplicity of biochemical effectors that can cause muscle damage and cumulative cell destruction in its prey. Despite previous investigations of <i>S. polymorpha</i> and other centipede venoms, there is a lack of information on the morphological and biochemical patterns elicited by their myotoxic effects. To elucidate these processes, this paper presents evidence of skeletal muscle ...[more]

PMID: 32536942

Similar Datasets

Project description:BackgroundMutations in the gene encoding ryanodine receptor type-1 (RYR1), the calcium ion (Ca (2+)) release channel in the sarcoplasmic reticulum (SR) of skeletal muscle, are linked to central core disease (CCD) and malignant hyperthermia (MH) susceptibility. We recently reported that mice lacking the skeletal isoform of calsequestrin (CASQ1-null), the primary Ca (2+) buffer in the SR of skeletal muscle and a modulator of RYR1 activity, exhibit lethal heat- and anesthetic-induced hypermetabolic episodes that resemble MH events in humans.MethodsWe compared ultrastructure, oxidative status, and contractile function in skeletal fibers of extensor digitorum longus (EDL) muscles in wild type (WT) and CASQ1-null mice at different ages (from 4 to 27 months) using structural, biochemical, and functional assays.ResultsAbout 25% of fibers in EDL muscles from CASQ1-null mice of 14 to 27 months of age exhibited large areas of structural disarray (named core-like regions), which were rarely observed in muscle from age-matched WT mice. To determine early events that may lead to the formation of cores, we analyzed EDL muscles from adult mice: at 4 to 6 months of age, CASQ1-null mice (compared to WT) displayed significantly reduced grip strength (40 ± 1 vs. 86 ± 1 mN/gr) and exhibited an increase in the percentage of damaged mitochondria (15.1% vs. 2.6%) and a decrease in average cross-sectional fiber area (approximately 37%) in EDL fibers. Finally, oxidative stress was also significantly increased (25% reduction in ratio between reduced and oxidized glutathione, or GSH/GSSG, and 35% increase in production of mitochondrial superoxide flashes). Providing ad libitum access to N-acetylcysteine in the drinking water for 2 months normalized GSH/GSSG ratio, reduced mitochondrial damage (down to 8.9%), and improved grip strength (from 46 ± 3 to 59 ± 2 mN/gr) in CASQ1-null mice.ConclusionsOur findings: 1) demonstrate that ablation of CASQ1 leads to enhanced oxidative stress, mitochondrial damage, and the formation of structural cores in skeletal muscle; 2) provide new insights in the pathogenic mechanisms that lead to damage/disappearance of mitochondria in cores; and 3) suggest that antioxidants may provide some therapeutic benefit in reducing mitochondrial damage, limiting the development of cores, and improving muscle function.

Project description:Chronic kidney disease (CKD) leads to increased skeletal muscle fatigue, weakness, and atrophy. Previous work has implicated mitochondria within the skeletal muscle as a mediator of muscle dysfunction in CKD; however, the mechanisms underlying mitochondrial dysfunction in CKD are not entirely known. The purpose of this study was to define the impact of uremic metabolites on mitochondrial energetics. Skeletal muscle mitochondria were isolated from C57BL/6N mice and exposed to vehicle (DMSO) or varying concentrations of uremic metabolites: indoxyl sulfate, indole-3-acetic-acid, l-kynurenine, and kynurenic acid. A comprehensive mitochondrial phenotyping platform that included assessments of mitochondrial oxidative phosphorylation (OXPHOS) conductance and respiratory capacity, hydrogen peroxide production (JH2O2), matrix dehydrogenase activity, electron transport system enzyme activity, and ATP synthase activity was employed. Uremic metabolite exposure resulted in a ~25-40% decrease in OXPHOS conductance across multiple substrate conditions (P < 0.05, n = 5-6/condition), as well as decreased ADP-stimulated and uncoupled respiratory capacity. ATP synthase activity was not impacted by uremic metabolites; however, a screen of matrix dehydrogenases indicated that malate and glutamate dehydrogenases were impaired by some, but not all, uremic metabolites. Assessments of electron transport system enzymes indicated that uremic metabolites significantly impair complex III and IV. Uremic metabolites resulted in increased JH2O2 under glutamate/malate, pyruvate/malate, and succinate conditions across multiple levels of energy demand (all P < 0.05, n = 4/group). Disruption of mitochondrial OXPHOS was confirmed by decreased respiratory capacity and elevated superoxide production in cultured myotubes. These findings provide direct evidence that uremic metabolites negatively impact skeletal muscle mitochondrial energetics, resulting in decreased energy transfer, impaired complex III and IV enzyme activity, and elevated oxidant production.

Dataset Information

Mitochondrial activity disruption and local muscle damage induced in mice by Scolopendra polymorpha venom.

Publications

Mitochondrial activity disruption and local muscle damage induced in mice by <i>Scolopendra polymorpha</i> venom.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure