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Open AccessArticle

Carnosine Activates Cellular Stress Response in Podocytes and Reduces Glycative and Lipoperoxidative Stress

1
Department of Biomedical and Biotechnological Sciences, University of Catania, 95124 Catania, Italy
2
Centre for Pediatric and Adolescent Medicine, University of Heidelberg, 69117 Heidelberg, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Shared senior authorship.
Biomedicines 2020, 8(6), 177; https://doi.org/10.3390/biomedicines8060177
Received: 11 May 2020 / Revised: 19 June 2020 / Accepted: 23 June 2020 / Published: 26 June 2020
(This article belongs to the Section Tumor Cell Biology)
Carnosine improves diabetic complications, including diabetic nephropathy, in in vivo models. To further understand the underlying mechanism of nephroprotection, we studied the effect of carnosine under glucose-induced stress on cellular stress response proteins in murine immortalized podocytes, essential for glomerular function. High-glucose stress initiated stress response by increasing intracellular heat shock protein 70 (Hsp70), sirtuin-1 (Sirt-1), thioredoxin (Trx), glutamate-cysteine ligase (gamma-glutamyl cysteine synthetase; γ-GCS) and heme oxygenase-1 (HO-1) in podocytes by 30–50% compared to untreated cells. Carnosine (1 mM) also induced a corresponding upregulation of these intracellular stress markers, which was even more prominent compared to glucose for Hsp70 (21%), γ-GCS and HO-1 (13% and 20%, respectively; all p < 0.001). Co-incubation of carnosine (1 mM) and glucose (25 mM) induced further upregulation of Hsp70 (84%), Sirt-1 (52%), Trx (35%), γ-GCS (90%) and HO-1 (73%) concentrations compared to untreated cells (all p < 0.001). The glucose-induced increase in 4-hydroxy-trans-2-nonenal (HNE) and protein carbonylation was reduced dose-dependently by carnosine by more than 50% (p < 0.001). Although podocytes tolerated high carnosine concentrations (10 mM), high carnosine levels only slightly increased Trx and γ-GCS (10% and 19%, respectively, compared to controls; p < 0.001), but not Hsp70, Sirt-1 and HO-1 proteins (p not significant), and did not modify the glucose-induced oxidative stress response. In podocytes, carnosine induced cellular stress tolerance and resilience pathways and was highly effective in reducing high-glucose-induced glycative and lipoperoxidative stress. Carnosine in moderate concentrations exerted a direct podocyte molecular protective action. View Full-Text
Keywords: carnosine; glucose; diabetic nephropathy cellular stress response; oxidative stress; vitagenes carnosine; glucose; diabetic nephropathy cellular stress response; oxidative stress; vitagenes
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MDPI and ACS Style

Scuto, M.; Trovato Salinaro, A.; Modafferi, S.; Polimeni, A.; Pfeffer, T.; Weigand, T.; Calabrese, V.; Schmitt, C.P.; Peters, V. Carnosine Activates Cellular Stress Response in Podocytes and Reduces Glycative and Lipoperoxidative Stress. Biomedicines 2020, 8, 177.

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