• Home
  • Search Results
  • Cyclophilin D-dependent mitochondrial permeability transition amplifies inflammatory reprogramming in endotoxemia.

Cyclophilin D-dependent mitochondrial permeability transition amplifies inflammatory reprogramming in endotoxemia.

FEBS open bio (2021-01-21)
Balazs Veres, Krisztian Eros, Csenge Antus, Nikoletta Kalman, Fruzsina Fonai, Peter Balazs Jakus, Eva Boros, Zoltan Hegedus, Istvan Nagy, Laszlo Tretter, Ferenc Gallyas, Balazs Sumegi

Microorganisms or LPS (lipopolysaccharide), an outer membrane component of Gram-negative bacteria, can induce a systemic inflammatory response that leads to sepsis, multiple organ dysfunction, and mortality. Here, we investigated the role of cyclophilin D (CypD)-dependent mitochondrial permeability transition (mPT) in the immunosuppressive phase of LPS-induced endotoxic shock. The liver plays an important role in immunity and organ dysfunction; therefore, we used liver RNA sequencing (RNA-seq) data, Ingenuity® Pathway Analysis (IPA ® ) to investigate the complex role of mPT formation in inflammatory reprogramming and disease progression. LPS induced significant changes in the expression of 2844 genes, affecting 179 pathways related to mitochondrial dysfunction, defective oxidative phosphorylation, nitric oxide (NO) and reactive oxygen species (ROS) accumulation, nuclear factor, erythroid 2 like 2 (Nrf2), Toll-like receptors (TLRs), and tumor necrosis factor α receptor (TNFR)-mediated processes in wild-type mice. The disruption of CypD reduced LPS-induced alterations in gene expression and pathways involving TNFRs and TLRs, in addition to improving survival and attenuating oxidative liver damage and the related NO- and ROS-producing pathways. CypD deficiency diminished the suppressive effect of LPS on mitochondrial function, nuclear- and mitochondrial-encoded genes, and mitochondrial DNA (mtDNA) quantity, which could be critical in improving survival. Our data propose that CypD-dependent mPT is an amplifier in inflammatory reprogramming and promotes disease progression. The mortality in human sepsis and shock is associated with mitochondrial dysfunction. Prevention of mPT by CypD disruption reduces inflammatory reprogramming, mitochondrial dysfunction, and lethality; therefore, CypD can be a novel drug target in endotoxic shock and related inflammatory diseases.

Product Number
Product Description

Anti-Rabbit IgG (whole molecule)–Peroxidase antibody produced in goat, affinity isolated antibody, buffered aqueous solution
ApopTag Plus Peroxidase In Situ Apoptosis Kit, The ApopTag Plus Peroxidase In Situ Apoptosis Detection Kit detects apoptotic cells by labeling & detecting DNA strand breaks by the indirect TUNEL method.
Phosphatase Inhibitor Cocktail Set III, Phosphatase Inhibitor Cocktail Set III is a ready to use cocktail of four phosphatase inhibitors for broad-spectrum inhibition of both serine/threonine and protein tyrosine phosphatases.
Anti-Nitrotyrosine Antibody, clone 1A6, clone 1A6, Upstate®, from mouse
Anti-GAPDH Antibody, from chicken, purified by affinity chromatography
Anti-4-Hydroxynonenal Antibody, serum, Chemicon®