Endonuclease G takes part in AIF-mediated caspase-independent apoptosis in Mycobacterium bovis-infected bovine macrophages

Abstract

Mycobacterium bovis, the causative agent of bovine tuberculosis encodes different virulence mechanisms to survive inside of host cells. One of the possible outcomes in this host–pathogen interaction is cell death. Previous results from our group showed that M. bovis induces a caspase-independent apoptosis in bovine macrophages with the possible participation of apoptosis inducing factor mitochondria associated 1 (AIFM1/AIF), a flavoprotein that functions as a cell-death regulator. However, contribution of other caspase-independent cell death mediators in M. bovis-infected macrophages is not known. In this study, we aimed to further characterize M. bovis-induced apoptosis, addressing Endonuclease G (Endo G) and Poly (ADP-ribose) polymerase 1 (PARP-1). In order to accomplish our objective, we infected bovine macrophages with M. bovis AN5 (MOI 10:1). Analysis of M. bovis-infected nuclear protein extracts by immunoblot, identified a 15- and 43-fold increase in concentration of mitochondrial proteins AIF and Endo G respectively. Interestingly, pretreatment of M. bovis-infected macrophages with cyclosporine A, a mitochondrial permeability transition pore inhibitor, abolished AIF and Endo G nuclear translocation. In addition, it also decreased macrophage DNA fragmentation to baseline and caused a 26.2% increase in bacterial viability. We also demonstrated that PARP-1 protein expression in macrophages did not change during M. bovis infection. Furthermore, pretreatment of M. bovis-infected bovine macrophages with 3-aminobenzamide, a PARP-1 inhibitor, did not change the proportion of macrophage DNA fragmentation. Our results suggest participation of Endo G, but not PARP-1, in M. bovis-induced macrophage apoptosis. To the best of our knowledge this is the first report associating Endo G with caspase-independent apoptosis induced by a member of the Mycobacterium tuberculosis complex.Electronic supplementary materialThe online version of this article (10.1186/s13567-018-0567-1) contains supplementary material, which is available to authorized users.

Baicalin modulates apoptosis via RAGE, MAPK, and AP-1 in vascular endothelial cells during Haemophilus parasuis invasion

“…35 However, whether baicalin could modulate apoptosis via RAGE, MAPK, and AP-1 in PAVECs during H. parasuis invasion has not been investigated. Previous research found apoptosis in monocytes during Streptococcus pneumoniae infection, 36 macrophages infected with Mycobacterium bovis 37,38 or Neisseria gonorrhoeae , 39 and HeLa cells infected by E. coli . 40 Whether PAVECs undergo apoptosis during H. parasuis infection remains unclear.…”

Mesenchymal stem cell‑derived extracellular vesicles prevent neural stem cell hypoxia injury via promoting miR‑210‑3p expression

“…In the nucleus, AIF activates endogenous nucleic acid endonuclease ( 41 ). AIF-dependent cell death cannot be reduced by caspase inhibitors, suggesting that AIF does not depend on caspases ( 42 ). Under hypoxic conditions, the expression of miR-210-3p in NSCs is upregulated ( 41 ).…”

Virus-Mediated Inhibition of Apoptosis in the Context of EBV-Associated Diseases: Molecular Mechanisms and Therapeutic Perspectives

“…Host Bcl-2 protein is the anti-apoptotic one [73]. It counteracts the induction of the intrinsic apoptosis pathway by preventing permeabilization of the outer mitochondrial membrane (OMM) and consequent release of pro-apoptotic molecules, such as cytochrome c [74], apoptosisinducing factor (AIF) [75], endonuclease G (Endo G) [76], and second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding (SMAC/DIABLO) protein [77]. BHRF1 shares 38% amino acid sequence homology with human Bcl-2.…”