p53 signalling controls cell cycle arrest and caspase-independent apoptosis in macrophages infected with pathogenicLeptospiraspecies

Abstract

SummaryPathogenic Leptospira species, the causative agents of leptospirosis, have been shown to induce macrophage apoptosis through caspaseindependent, mitochondrion-related apoptosis inducing factor (AIF) and endonuclease G (EndoG), but the signalling pathway leading to AIF/EndoGbased macrophage apoptosis remains unknown. Here we show that infection of Leptospira interrogans caused a rapid increase in reactive oxygen species (ROS), DNA damage, and intranuclear foci of 53BP1 and phosphorylation of H2AX (two DNA damage indicators) in wild-type p53-containing mouse macrophages and p53-deficient human macrophages. Most leptospire-infected cells stayed at the G 1 phase, whereas depletion or inhibition of p53 caused a decrease of the G1-phase cells and the early apoptotic ratios. Infection with spirochaetes stimulated a persistent activation of p53 and an early activation of Akt through phosphorylation. The intranuclear translocation of p53, increased expression of p53-dependent p21 Cip1/WAF1

Germacrone inhibits the proliferation of glioma cells by promoting apoptosis and inducing cell cycle arrest

“…It is well known that the protein p53, encoded by the TP53 gene, has a crucial role in multi-cellular organisms, where it regulates apoptosis and the cell cycle (15). When a cell is exposed to damage, p53 is activated and inhibits various downstream target genes involved in apoptosis and cell cycle arrest, including bax, p53-upregulated modulator of apoptosis (PUMA), bcl-2 and p21 (16).…”

RETRACTED: ChpK and MazF of the toxin–antitoxin modules are involved in the virulence of Leptospira interrogans during infection

“…Wildtype pCMV-Tag2C-transfected THP-1 cells and normal THP-1 cells without transfection were used as controls. Besides, the THP-1 cells for chpK or mazF gene transfection were pretreated with 100 mM of the pan-caspase inhibitor Z-VAD-FMK (Sigma) and then detected by flow cytometry as above to distinguish necrosis from caspase-dependent apoptosis [37].…”

The role of reactive oxygen intermediates in the intracellular fate of Leptospira interrogans in the macrophages of different hosts

“…Mononuclear macrophages and neutrophils have been shown to phagocytose leptospires, but only the former can kill the phagocytosed intracellular leptospires [11, 12], indicating that mononuclear macrophages are much more important than neutrophils in the defense mechanisms against leptospiral infection. Our previous study showed that L .…”