Shiga Toxin 2-Induced Endoplasmic Reticulum Stress Is Minimized by Activated Protein C but Does Not Correlate with Lethal Kidney Injury

“…application of a single high dose of Stx2 alone ( 32 ), or by multiple i.p. applications of sub-lethal doses of Stx2 ( 33 , 39 , 40 ). In most studies, injection of Stx alone appeared to be insufficient to induce HUS-like disease in mice ( 31 , 32 , 41 ).…”

“…The intoxicated cells were susceptible to the cytotoxic action of Stxs with significant cleavage of poly(ADP-ribose) polymerase (PARP), an enzyme primarily involved in DNA repair and induction of programmed cell death [ 104 ]. Parello et al observed that prolonged renal ER stress was capable of contributing to apoptosis in murine models of Stx2-induced kidney injury, although the downregulation of ER stress induced by Stx2 was not sufficient to prevent renal cytotoxicity in mice [ 105 ]. When Caco-2 cells, a cultured line of human enterocytes, were exposed to Stx2, autophagic cell death preceding apoptosis was promoted through ER stress [ 106 ].…”

“…Cell death can occur by apoptosis or necrosis. [12][13][14] The mechanism of cell death can influence adjacent tissue. Apoptosis does not elicit inflammation when cells are cleared by phagocytosis.…”