Biology subjects

Mericskay, M.

Publications and source records attributed to Mericskay, M..

3 recordsLinked to original sources

bioRxiv2024

Nicotinamide riboside: A promising therapy for MI-induced acute kidney injury by upregulating nicotinamide phosphoribosyltransferase-mediated NAD levels

BackgroundCardiorenal syndrome (CRS) type 1 is characterized by the development of acute kidney injury (AKI) following acute cardiac illness and notably acute myocardial infarction (MI). AKI is considered an independent risk factor increasing mortality rate substantially. Nicotinamide dinucleotide (NAD) is an important coenzyme in energy metabolism and oxidative phosphorylation and in its oxidized form, a substrate for multiple NAD+-dependent enzymes such as Sirtuins and poly-ADP ribose polymerases. Decreased cardiac NAD levels along with a down-regulation of the nicotinamide phosphoribosyl transferase (NAMPT) have been reported following MI. A compensatory upregulation in nicotinamide riboside kinase (NMRK) 2, an NAD+ biosynthetic enzyme that uses nicotinamide riboside (NR) to generate NAD+ takes place in the heart after MI but the impact on kidney NAD metabolism and function has not been addressed before. MethodsMI was induced by ligating the left anterior descending coronary artery in 2 months old C57BL6/J mice, followed by the administration of NR (IP injection, 400mg/kg/day) for four and seven days. We hypothesized that NR treatment could be a potential promising therapy for MI-induced AKI. ResultsOur findings showed no significant improvement in cardiac ejection fraction following NR treatment at days 4 and 7 post-MI, whereas kidney functions were enhanced and morphological alterations and cell death decreased. The observed renal protection seems to be mediated by an up-regulation of NAMPT-mediated increase in renal NAD levels, notably in distal tubules. ConclusionOur findings indicate that NR could be a potential promising therapy for AKI following an early stage of MI.

pharmacology and toxicology↗

bioRxiv2020

HIGH FAT DIET STIMULATES BETA-OXIDATION, ALTERS ELECTRICAL PROPERTIES AND INDUCES ADIPOGENICITY OF ATRIA IN OBESE MICE

Metabolic disorders such as obesity are risk factors of atrial fibrillation, not only by sharing comorbidities but likely through their direct impact on atria, notably its adipogenicity. Here, we submitted mice that lack cardiac adipose tissue to a high fat diet and first studied the atrial metabolomic and lipidomic phenotypes using liquid chromatography-mass spectrometry. We found an increased consumption of free fatty acid by the beta-oxidation and an accumulation of long-chain lipids in atria of obese mice. Free fatty acid was the main substrate of mitochondrial respiration studied in the saponin-permeabilized atrial muscle. Conducted action potential recorded in atrial trabeculae was short, and ATP-sensitive potassium current was increased in perforated patch-clamp atrial myocytes of obese mice. There was histological and phenotypical evidence for an accumulation of adipose tissue in obese mice atria. Thus, an obesogenic diet transforms the energy metabolism, causes fat accumulation and induces electrical remodeling of atria myocardium. HIGHLIGHTS- Untargeted metabolomic and lipidomic analysis revealed that a high fat diet induces profound transformation of atrial energy metabolism with beta-oxidation activation and long-chain lipid accumulation. - Mitochondria respiration studied in atrial myocardial trabecula preferentially used Palmitoyl-CoA as energy substrate in obese mice. - Atria of obese mice become vulnerable to atrial fibrillation and show short action potential due to the activation of K-ATP dependent potassium current. - Adipocytes and fat molecular markers were detected in atria of obese mice together with an inflammatory profile consistence with a myocardial accumulation of fat.

physiology↗

bioRxiv2019

Mechanical and molecular parameters that influence the tendon differentiation potential of C3H10T1/2 cells in 2D- and 3D-culture systems

One of the main challenges in tendon field relies in the understanding of regulators of the tendon differentiation program. The optimum culture conditions that favor tendon cell differentiation are not identified. Mesenchymal stem cells present the ability to differentiate into multiple lineages in cultures under different cues ranging from chemical treatment to physical constraints. We analyzed the tendon differentiation potential of C3H10T1/2 cells, a murine cell line of mesenchymal stem cells, upon different 2D- and 3D-culture conditions. We observed that C3H10T1/2 cells cultured in 2D conditions on silicone substrate were more prone to tendon differentiation assessed with the expression of the tendon markers Scx, Col1a1 and Tnmd as compared to cells cultured on plastic substrate. 3D fibrin environment was more favorable for Scx and Col1a1 expression compared to 2D-cultures. We also identified TGF{beta}2 as a negative regulator of Tnmd expression in C3H10T1/2 cells in 2D- and 3D-cultures. Altogether, our results provide us with a better understanding of the culture conditions that promote tendon gene expression and identify mechanical and molecular parameters on which we could play to define the optimum culture conditions that favor tenogenic differentiation in mesenchymal stem cells.

developmental biology↗