Klotho attenuates angiotensin II‑induced cardiotoxicity through suppression of necroptosis and oxidative stress.

Molecular Medicine Reports
Shasha YuYingxian Sun

Abstract

Hyperglycemia is known to lead to cardiac injury and inflammation through the reactive oxygen species (ROS)‑Toll‑like receptor 4 (TLR4)‑necroptosis pathway. Similarly, angiotensin II (Ang II) activates the TLR4‑nuclear factor κB (NF‑κB) p65 pathway, while the protein Klotho is known to inhibit this pathway, protecting cardiac cells from Ang II‑induced injury. However, there is currently a lack of data on whether necroptosis participates in Ang II‑induced cardiac injury and whether the Klotho protein has an effect on this process. The present study aimed to explore whether inhibition of the TLR4/NF‑κB p65 necroptosis pathway is involved in the Klotho protein‑mediated protection against the Ang II‑induced cardiac injury and inflammation. H9c2 cardiac cells were incubated with 0.01 mM Ang II. Western blotting was used to assess the expression of receptor‑interacting protein kinase 3 (RIP3), mixed‑lineage kinase domain‑like protein (MLKL), TLR4 and NF‑κB p65. The present study also assessed injury indexes: Inflammatory cytokine expression, mitochondrial membrane potential (ΔΨm), apoptosis, ROS production and cell viability. The expression of TLR4, phosphorylated (p)‑NF‑κB p65, RIP3 and MLKL were increased by incubation with Ang II ...Continue Reading

Methods Mentioned

BETA
ELISA
Protein Assay
flow cytometry

Software Mentioned

Pro ® Plus
ImageJ
SPSS
FlowJo
Image

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