Inhibition of aldose-reductase-2 by a benzofuroxane derivative bf-5m increases the expression of kcne1, kcnq1 in high glucose cultured H9c2 cardiac cells and sudden cardiac death

Trotta, Maria Consiglia; Salerno, Monica; Brigida, Anna Lisa; Monda, Vincenzo; Messina, Antonietta; Fiore, Carmela; Avola, Roberto; Bernardini, Renato; Sessa, Francesco; Marsala, Gabriella; Zanghì, G; Messina, Giovanni; D’Amico, Michele; Filippo, Clara Di

doi:10.18632/oncotarget.23270

Cited by 6 publications

(14 citation statements)

References 42 publications

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“…3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay was used to measure cell viability . Briefly, the addition of MTT solution (1:10 in culture medium) to each well was followed by a 3‐hour incubation at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…No. 1187358000) and centrifuged at 13 800 g for 10 minutes at 4°C, to purify the protein supernatants from nucleic acids . Total protein concentration was determined following the Bio‐Rad protein assay protocol (Bio‐Rad Laboratories; Cat.…”

Section: Methodsmentioning

confidence: 99%

“…3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure cell viability. 14…”

Section: Cell Viability Assaymentioning

confidence: 99%

“…This is characterized by modifications of the ATP‐sensitive potassium (KATP) channels, important sensors for cardiac action potential repolarization and modifications of connexin 43 (Cnx43), the main constitutional protein of the gap junctions into the ventricle . These modifications are induced through changes in the local expression of microRNA‐1 (miR‐1) which targets both Cnx43 and the potassium voltage‐gated channel subfamily Q member 1 (KCNQ1 or Kv7.1), even if their combined role is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

“…(miR-1) 9,10 which targets both Cnx43 and the potassium voltagegated channel subfamily Q member 1 (KCNQ1 or Kv7.1), [11][12][13][14] even if their combined role is not fully understood.…”

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confidence: 99%

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Telmisartan cardioprotects from the ischaemic/hypoxic damage through a miR‐1‐dependent pathway

Trotta

Ferraro

Messina

et al. 2019

J Cellular Molecular Medi

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The aim of this study was to investigate whether telmisartan protects the heart from the ischaemia/reperfusion damage through a local microRNA‐1 modulation. Studies on the myocardial ischaemia/reperfusion injury in vivo and on the cardiomyocyte hypoxia/reoxygenation damage in vitro were done. In vivo, male Sprague‐Dawley rats administered for 3 weeks with telmisartan 12 mg/kg/d by gastric gavage underwent ischaemia/reperfusion of the left descending coronary artery. In these rats, infarct size measurement, ELISA, immunohistochemistry (IHC) and reverse transcriptase real‐time polymerase chain reaction showed that expressions of connexin 43, potassium voltage‐gated channel subfamily Q member 1 and the protein Bcl‐2 were significantly increased by telmisartan in the reperfused myocardium, paralleled by microRNA‐1 down‐regulation. In vitro, the transfection of cardiomyocytes with microRNA‐1 reduced the expressions of connexin 43, potassium voltage‐gated channel subfamily Q member 1 and Bcl‐2 in the cells. Telmisartan (50 µmol/L) 60 minutes before hypoxia/reoxygenation, while not affecting the levels of miR‐1 in transfected cells in normoxic condition, almost abolished the increment of miR‐1 induced by the hypoxia/reoxygenation to transfected cells. All together, telmisartan cardioprotected against the myocardial damage through the microRNA‐1 modulation, and consequent modifications of its downstream target connexin 43, potassium voltage‐gated channel subfamily Q member 1 and Bcl‐2.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure cell viability. 14…”

Section: Cell Viability Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…(miR-1) 9,10 which targets both Cnx43 and the potassium voltagegated channel subfamily Q member 1 (KCNQ1 or Kv7.1), [11][12][13][14] even if their combined role is not fully understood.…”

mentioning

confidence: 99%

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Telmisartan cardioprotects from the ischaemic/hypoxic damage through a miR‐1‐dependent pathway

Trotta

Ferraro

Messina

et al. 2019

J Cellular Molecular Medi

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Resolvin D1 reduces mitochondrial damage to photoreceptors of primary retinal cells exposed to high glucose

Trotta

Pieretti

Petrillo

et al. 2019

Journal Cellular Physiology

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No study has investigated the interaction of Resolvin D1 (RvD1) with mitochondrial damage of retinal cells caused by diabetes. This study aims to investigate the effects of RvD1 (50 nM) on morphological and biochemical indicators of mitochondrial damage in primary retinal cells exposed to 30 mM D-glucose high glucose (HG). HG-cells exhibited photoreceptor damage characterized by short and small mitochondria with prevalent mitochondrial disruption, fragmentation, and aggregation. The cells had low mitochondrial transporters TIMM44 and TOMM40, Connexin 43, NAD/NADH ratio, and ATP levels, whereas increased cytosolic cytochrome c. Moreover, they expressed high cytosolic metalloproteinase matrix metallopeptidase 9 (MMP-9) and MMP-2 activity.HG-cells treated with RvD1 (50 nM) showed reduced reactive oxygen species levels, improved mitochondrial morphology and function, promoted mitochondrial DNA repair by OGG1, and reduced cell apoptosis and metalloproteinase activity. Therefore, RvD1 induces protection from high glucose-load to the retinal cell and promotes their survival by decreasing cytosolic MMP and mitochondrial damage. K E Y W O R D SALX/FPR2 receptor, hyperglycemia, mitochondrial damage, primary retinal cells, resolvin D1

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The activation of retinal HCA2 receptors by systemic beta-hydroxybutyrate inhibits diabetic retinal damage through reduction of endoplasmic reticulum stress and the NLRP3 inflammasome

et al. 2019

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ObjectiveThe role of the hydroxycarboxylic acid receptor 2 (HCA2) in the retinal damage induced by diabetes has never been explored. In this context, the present study highlights an upregulation of retinal HCA2 receptors in diabetic C57BL6J mice. Moreover, we illustrate that HCA2 receptors exert an anti-inflammatory effect on the retinal damage induced by diabetes when activated by the endogenous ligand β-hydroxybutyrate,MethodologySeven-to-10-week-old C57BL6J mice were rendered diabetic by a single intraperitoneal injection of streptozotocin (75 mg/kg of body weight) and monitored intermittently over a 10-week period extending from the initial diabetes assessment. Mice with a fasting blood glucose level higher than 250 mg/dl for 2 consecutive weeks after streptozotocin injection were treated twice a week with intraperitoneal injections of 25-50-100 mg/kg β-hydroxybutyrate.ResultsInterestingly, while the retinal endoplasmic reticulum stress markers (pPERK, pIRE1, ATF-6α) were elevated in diabetic C57BL6J mice, their levels were significantly reduced by the systemic intraperitoneal treatment with 50 mg/kg and 100 mg/kg β-hydroxybutyrate. These mice also exhibited high NLRP3 inflammasome activity and proinflammatory cytokine levels. In fact, the elevated levels of retinal NLRP3 inflammasome activation markers (NLRP3, ASC, caspase-1) and of the relative proinflammatory cytokines (IL-1β, IL-18) were significantly reduced by 50 mg/kg and 100 mg/kg β-hydroxybutyrate treatment. These doses also reduced the high apoptotic cell number exhibited by the diabetic mice in the retinal outer nuclear layer (ONL) and increased the ONL low connexin 43 expression, leading to an improvement in retinal permeability and homeostasis.ConclusionsThese data suggest that the systemic treatment of diabetic C57BL6J mice with BHB activates retinal HCA2 and inhibits local damage.

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Inhibition of aldose-reductase-2 by a benzofuroxane derivative bf-5m increases the expression of kcne1, kcnq1 in high glucose cultured H9c2 cardiac cells and sudden cardiac death

Cited by 6 publications

References 42 publications

Telmisartan cardioprotects from the ischaemic/hypoxic damage through a miR‐1‐dependent pathway

Telmisartan cardioprotects from the ischaemic/hypoxic damage through a miR‐1‐dependent pathway

Resolvin D1 reduces mitochondrial damage to photoreceptors of primary retinal cells exposed to high glucose

The activation of retinal HCA2 receptors by systemic beta-hydroxybutyrate inhibits diabetic retinal damage through reduction of endoplasmic reticulum stress and the NLRP3 inflammasome

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