Search

Autophagy and apoptosis are critical for controllingToxoplasma gondii(T. gondii) infection.T. gondiiinfection during pregnancy can damage the fetus and cause birth defects; however, the molecular mechanisms of this process are poorly understood. This study aims to determine the activities of autophagy and apoptosis as well as their regulatory mechanisms duringT. gondiiinfection by using human umbilical cord mesenchymal stem cells (hUC-MSCs) as a model of congenital diseases. LC3B, a hallmark protein of autophagy was incrementally upregulated with the infection duration, whereas p62 was downregulated inT. gondii-infected hUC-MSCs. Concurrent to this result, the invasion ofT. gondiiinto hUC-MSCs increased in a time-dependent manner. The expression levels of Bcl−2 family proteins including Bcl−2, Bcl−xL, Bim, Bax, Bid and Bak were not altered; however, Mcl−1 levels in hUC-MSCs were dramatically decreased uponT. gondiiinfection. In addition, at 24 h post-infection, cleaved PARP and cleaved caspase-3 protein levels were elevated in hUC-MSCs. Importantly, Mcl−1 overexpression reduced the levels of autophagy- and apoptosis-related proteins inT. gondii-infected hUC-MSCs. Mcl−1 proteins were primarily expressed in the fraction containing mitochondria and strongly interacted with Beclin-1 under normal conditions; however, these interactions were remarkably attenuated byT. gondiiinfection. These results suggest that mitochondrial Mcl−1 is an essential signaling mediator regulating the activation of autophagy and apoptosis duringT. gondiiinfection. [ABSTRACT FROM PUBLISHER]