The effects of buthionine sulfoximine treatment on diaphragm contractility and SERCA pump function in adult and middle aged rats

Smith, Ian D.; Vigna, Chris; Levy, Andrew; Denniss, Steven G; Rush, James W. E.; Tupling, A. Russell

doi:10.14814/phy2.12547

Cited by 8 publications

(7 citation statements)

References 58 publications

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“…Recent studies demonstrated that inflammatory lesions also played an important role in myocardial ischemia-reperfusion injury (25,26). IL-6 is a cytokine that is mainly secreted from monocytes, macrophages and T/B lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of gastrodin on myocardial ischemia‑reperfusion injury and the expression of Bax and Bcl‑2

et al. 2019

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The protective effects of gastrodin on myocardial ischemia-reperfusion injury in rats and the underlying mechanism were investigated. Sprague Dawley (SD) rats were randomly divided into three groups, of which the gastrodin group was treated with gastrodin, and the other two groups were treated with normal saline. In the myocardial ischemia-reperfusion model group, myocardial ischemia was induced by ligation of the left anterior descending coronary artery, and myocardial reperfusion was performed by ligature removal. Only thread without ligation for the sham operation group was conducted. The rats were euthanized 8 days after surgery. Heart tissues were harvested and used for measurement of apoptotic rate and expression levels of apoptosis-related proteins. Serum levels of cytokines were measured also using blood samples. Compared with the myocardial ischemia-reperfusion model group, significant reduction of cardiomyocyte apoptosis was observed in the gastrodin group (P<0.05). In the gastrodin group, the protein and mRNA expression levels for Bax and activated caspase-3 decreased, while for Bcl-2 increased (P<0.05). Gastrodin can downregulate inflammatory cytokines (P<0.05) and upregulate anti-inflammatory cytokines such as IL-10 (P<0.05) in serum of SD rats. Therefore, gastrodin played a protective role in myocardial ischemia-reperfusion injury by regulating the expression levels of apoptosis-related signaling proteins and inflammatory cytokines.

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Section: Discussionmentioning

confidence: 99%

Protective effect of gastrodin on myocardial ischemia‑reperfusion injury and the expression of Bax and Bcl‑2

et al. 2019

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“…GSH exists as the biologically active reduced-thiol form, and its oxidation to GSSG is associated with oxidative stress (OS). The GSH/GSSG ratio is around 100/1; when GSSG increases, this ratio decreases causing an oxidative shift in the cellular redox state[ 31 ]. Intestinal GSH redox homeostasis is maintained by de novo synthesis[ 32 ], regeneration from GSSG[ 33 ] and GSH uptake that derives from the dietary intake and mainly from the biliary output because the bile is enriched in GSH (1-2 mmol/L)[ 34 , 35 ].…”

Section: Gsh Synthesis and Its Physiological Role In The Intestinementioning

confidence: 99%

Glutathione depleting drugs, antioxidants and intestinal calcium absorption

Moine¹,

Rivoira²,

Barboza³

et al. 2018

WJG

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Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2+ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca2+ absorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxidative/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca2+ transport or the paracellular Ca2+ route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca2+ pathway are decreased. The flavonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca2+ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca2+ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca2+ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety, pharmacokinetics and pharmacodynamics of them.

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“…The mice lacking Sod1 show increased oxidative damage to DNA, proteins and lipids in skeletal muscle, and other tissues that is associated with muscle atrophy and functional decline. More specifically, these muscles show increased 3‐nitrotyrosine content, which is known to disturb SR protein function and the muscle contractile force …”

Section: Introductionmentioning

confidence: 99%

Oxidative stress‐induced dysregulation of excitation–contraction coupling contributes to muscle weakness

Qaisar

Bhaskaran

Premkumar

et al. 2018

J cachexia sarcopenia muscle

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BackgroundWe have previously shown that the deletion of the superoxide scavenger, CuZn superoxide dismutase, in mice (Sod1 −/− mice) results in increased oxidative stress and an accelerated loss of skeletal muscle mass and force that mirror the changes seen in old control mice. The goal of this study is to define the effect of oxidative stress and ageing on muscle weakness and the Excitation Contraction (EC) coupling machinery in age‐matched adult (8–10 months) wild‐type (WT) and Sod1 −/− mice in comparison with old (25–28 months) WT mice.Methods In vitro contractile assays were used to measure muscle contractile parameters. The activity of the sarcoplasmic reticulum Ca2+ ATPase (SERCA) pump was measured using an NADH‐linked enzyme assay. Immunoblotting and immunofluorescence techniques were used to measure protein expression, and real‐time reverse transcription PCR was used to measure gene expression.ResultsThe specific force generated by the extensor digitorum longus muscle was reduced in the Sod1 −/− and old WT mice compared with young WT mice along with significant prolongation of time to peak force, increased half relaxation time, and disruption of intracellular calcium handling. The maximal activity of the SERCA calcium uptake pump was significantly reduced in gastrocnemius muscle from both old WT (≈14%) and adult Sod1 −/− (≈33%) mice compared with young WT mice along with increased expression of sarcolipin, a known inhibitor of SERCA activity. Protein levels of the voltage sensor and calcium uptake channel proteins dihydropyridine receptor α1 and SERCA2 were significantly elevated (≈45% and ≈57%, respectively), while the ratio of calstabin, a channel stabilizing protein, to ryanodine receptor was significantly reduced (≈21%) in Sod1 −/− mice compared with young WT mice. The changes in calcium handling were accompanied by substantially elevated levels of global protein carbonylation and lipid peroxidation.ConclusionsOur data suggest that the muscle weakness in Sod1 −/− and old WT mice is in part driven by reactive oxygen species‐mediated EC uncoupling and supports a role for reduced SERCA pump activity in compromised muscle function. The novel quantitative mechanistic data provided here can lead to potential therapeutic interventions of SERCA dysfunction for sarcopenia and muscle diseases.

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The effects of buthionine sulfoximine treatment on diaphragm contractility and SERCA pump function in adult and middle aged rats

Cited by 8 publications

References 58 publications

Protective effect of gastrodin on myocardial ischemia‑reperfusion injury and the expression of Bax and Bcl‑2

Protective effect of gastrodin on myocardial ischemia‑reperfusion injury and the expression of Bax and Bcl‑2

Glutathione depleting drugs, antioxidants and intestinal calcium absorption

Oxidative stress‐induced dysregulation of excitation–contraction coupling contributes to muscle weakness

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