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NF-κB transcriptional inhibition ameliorates cisplatin-induced acute kidney injury (AKI)


Ozkok, Abdullah; Ravichandran, Kameswaran; Wang, Qian; Galešić Ljubanović, Danica; Edelstein, Charles L.
NF-κB transcriptional inhibition ameliorates cisplatin-induced acute kidney injury (AKI) // Toxicology Letters, 240 (2016), 1; 105-113 doi:10.1016/j.toxlet.2015.10.028 (međunarodna recenzija, članak, znanstveni)


Naslov
NF-κB transcriptional inhibition ameliorates cisplatin-induced acute kidney injury (AKI)

Autori
Ozkok, Abdullah ; Ravichandran, Kameswaran ; Wang, Qian ; Galešić Ljubanović, Danica ; Edelstein, Charles L.

Izvornik
Toxicology Letters (0378-4274) 240 (2016), 1; 105-113

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
NF-κB ; cisplatin-induced acute kidney injury (AKI)

Sažetak
The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) cell signaling pathway is important in inflammation and cell survival. Inflammation and cell death in the kidney are features of cisplatin-induced AKI. While it is known that cisplatin induces NF-κB signaling in the kidney, the NF-κB responsive genes and the effect of direct NF-κB transcriptional inhibition in cisplatin-induced AKI is not known. Mice injected with cisplatin, 25mg/kg, developed AKI, acute tubular necrosis (ATN) and apoptosis on day 3. Mice were treated with JSH-23 (20 or 40 mg/kg) which directly affects NF-κB transcriptional activity. Kidney function, tubular injury (ATN, serum neutrophil gelatinase-associated lipocalin [NGAL], but not apoptosis) and myeloperoxidase (MPO) activity were significantly improved by JSH-23 (40 mg/kg). Sixty one NF-κB responsive genes were increased by cisplatin of which 21 genes were decreased by JSH-23. Genes that were decreased by JSH-23 that are known to play a role in cisplatin-induced AKI were IL-10, IFN-γ, chemokine [C-C motif] ligand 2 (CCL2) and caspase-1. Another gene, caspase recruitment domain family, member 11 (CARD11), not previously known to play a role in AKI, was increased more than 20-fold and completely inhibited by JSH-23. CXCL1 and TNF-α, known mediators of cisplatin- induced AKI, were decreased by JSH-23. RIPK1 and 3, receptor-interacting serine/threonine-protein kinases, that play an important role in necroptosis, were decreased by JSH-23. In mouse proximal tubule cells in culture, JSH-23 resulted in an increase in apoptosis suggesting that the mechanism of protection against AKI by JSH-23 is not due to a direct effect on proximal tubules. In conclusion, NF-κB transcriptional inhibition in cisplatin-induced AKI ameliorates kidney function and ATN without a significant effect on apoptosis and is associated with a decrease pro- inflammatory mediators and CARD11.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti



POVEZANOST RADA


Projekt / tema
198-0000000-3355 - Značaj morfoloških čimbenika u dijagnostici, terapiji i prognozi FSGS (Danica Galešić-Ljubanović, )

Ustanove
Medicinski fakultet, Zagreb,
Klinička bolnica "Dubrava"

Autor s matičnim brojem:
Danica Galešić-Ljubanović, (203674)

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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