Examinando por Autor "Schlabs, Farina L."

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    NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging
    (Elsevier, 2025-06-25) Chubanava, Sabina; Karavaeva, Iuliia; Ehrlich, Amy M.; Justicia, Roger M.; Basse, Astrid L.; Kulik, Ivan; Dalbram, Emilie; Ahwazi, Danial; Heaselgrave, Samuel R.; Trost, Kajetan; Stocks, Ben; Hodek, Ondrej; Rodrigues, Raissa N.; Havelund, Jesper F.; Schlabs, Farina L.; Larsen, Steen; Yonamine, Caio Y.; Henríquez-Olguín, Carlos; Giustarini, Daniela; Rossi, Ranieri; Gerhart-Hines, Zachary; Moritz, Thomas; Zierath, Juleen R.; Sakamoto, Kei; Jensen, Thomas E.; Færgeman, Nils J.; Lavery, Gareth G.; Deshmukh, Atul S.; Treebak, Jonas T.
    Nicotinamide adenine dinucleotide (NAD) is a ubiquitous electron carrier essential for energy metabolism and post-translational modification of numerous regulatory proteins. Dysregulations of NAD metabolism are widely regarded as detrimental to health, with NAD depletion commonly implicated in aging. However, the extent to which cellular NAD concentration can decline without adverse consequences remains unclear. To investigate this, we generated a mouse model in which nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD+ biosynthesis was disrupted in adult skeletal muscle. The intervention resulted in an 85% reduction in muscle NAD+ abundance while maintaining tissue integrity and functionality, as demonstrated by preserved muscle morphology, contractility, and exercise tolerance. This absence of functional impairments was further supported by intact mitochondrial respiratory capacity and unaltered muscle transcriptomic and proteomic profiles. Furthermore, lifelong NAD depletion did not accelerate muscle aging or impair whole-body metabolism. Collectively, these findings suggest that NAD depletion does not contribute to age-related decline in skeletal muscle function.
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    Ítem
    Revisiting insulin-stimulated hydrogen peroxide dynamics reveals a cytosolic reductive shift in skeletal muscle
    (Elsevier, 2025-04-25) Henríquez-Olguín, Carlos; Gallero, Samantha; Reddy, Anita; Persson, Kaspar W.; Schlabs, Farina L.; Voldstedlund, Christian T.; Valentinaviciute, Gintare; Meneses-Valdés, Roberto; Sigvardsen, Casper M.; Kiens, Bente; Chouchani, Edward T.; Richter, Erik A.; Jensen, Thomas E.
    The intracellular redox state is crucial for insulin responses in peripheral tissues. Despite the longstanding belief that insulin signaling increases hydrogen peroxide (H2O2) production leading to reversible oxidation of cysteine thiols, evidence is inconsistent and rarely involves human tissues. In this study, we systematically investigated insulin-dependent changes in subcellular H2O2 levels and reversible cysteine modifications across mouse and human skeletal muscle models. Utilizing advanced redox tools including genetically encoded H2O2 sensors and non-reducing immunoblotting we consistently observed no increase in subcellular H2O2 levels following insulin stimulation. Instead, stoichiometric cysteine proteome analyses revealed a selective pro-reductive shift in cysteine modifications affecting insulin transduction related proteins, including Cys179 on GSK3β and Cys416 on Ras and Rab Interactor 2 (RIN2). Our findings challenge the prevailing notion that insulin promotes H2O2 generation in skeletal muscle and suggest that an insulin-stimulated pro-reductive shift modulates certain aspects of insulin signal transduction.