Carnosine activates cellular stress response in podocytes and reduces glycative and lipoperoxidative stress
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, ess...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
26 June 2020
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| In: |
Biomedicines
Year: 2020, Volume: 8, Issue: 6 |
| ISSN: | 2227-9059 |
| DOI: | 10.3390/biomedicines8060177 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/biomedicines8060177 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2227-9059/8/6/177 
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| Author Notes: | Maria Scuto, Angela Trovato Salinaro, Sergio Modafferi, Alessandra Polimeni, Tilman Pfeffer, Tim Weigand, Vittorio Calabrese, Claus Peter Schmitt and Verena Peters |
| Summary: | 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. |
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| Item Description: | Gesehen am 26.08.2020 |
| Physical Description: | Online Resource |
| ISSN: | 2227-9059 |
| DOI: | 10.3390/biomedicines8060177 |