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Porcine parvovirus (PPV) is a major virus that leads to fetal death in swine. However, the effects of PPV infection on sows are poorly understood. The aim of this study was to investigate the effects of PPV on porcine steroidogenic luteal cells (SLCs) survival and functions and underlying mechanisms. In vivo experiment results showed that artificial infection of PPV significantly reduced the concentration of serum progesterone and induced histopathological lesions and SLCs apoptosis in porcine corpora luteum. In in vitro cultured primary porcine SLCs, PPV could infect and replicate in SLCs and induced SLCs apoptosis through mitochondria, but not the death receptor, mediated apoptosis pathway. Meanwhile, PPV infection also decreased progesterone production in SLCs. Moreover, PPV infection could increase active p53 transcriptional activity and protein expression as well as promoting p53 translocation to nucleus. Using the p53-specific pharmacological inhibitor (pifithrin-α) and siRNA could partially attenuate PPV-induced Bax upregulation, caspase-3 activation, apoptosis, and the reduction of progesterone production in primary porcine SLCs. Furthermore, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was also increased in PPV-infected SLCs. Pretreatment with p38 MAPK inhibitor (SB203580) suppressed PPV-induced p53 accumulation and translocation, SLCs apoptosis, and progesterone production reduction. In summary, these findings indicate that PPV could induce SLCs apoptosis and a decrease of progesterone production in vivo and in vitro via p38 MAPK signaling and p53-dependent mitochondrial pathway, which provides the potential clinical therapy methods for PPV infection.

Porcine parvovirus (PPV) infection has been reported to induce the cytopathic effects (CPE) in some special host cells and contribute the occurrence of porcine parvovirus disease, but the molecular mechanisms underlying PPV-induced CPE are not clear. In this study, we investigated the morphological and molecular changes of porcine kidney cell line (PK-15 cells) infected with PPV. The results showed that PPV infection inhibited the viability of PK-15 cells in a time and concentration dependent manner. PPV infection induced typical apoptotic features including chromatin condensation, apoptotic body formation, nuclear fragmentation, and Annexin V-binding activity. Further studies showed that Bax was increased and translocated to mitochondria, whereas Bcl-2 was decreased in PPV-infected cells, which caused mitochondrial outer-membrane permeabilization, resulting in the release of mitochondrial cytochrome c, followed by caspase-9 and caspase-3 activation. However, the expression of Fas and Fas ligand (FasL) did not appear significant changes in the process of PPV-induced apoptosis. Moreover, PPV infection activated p53 signaling, which was involved in the activation of apoptotic signaling induced by PPV infection via regulation of Bax and Bcl-2. Taken together, our results demonstrated that PPV infection induced apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated apoptosis pathway. This study may contribute to shed light on the molecular pathogenesis of PPV infection., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The indolizidine alkaloid swainsonine (SW) has been reported to impair placentae and ultimately cause abortion in pregnant goats. Up to now, however, the precise effects of SW on goat trophoblast cells (GTCs) are still unclear. In this study, the cytotoxicity effects of SW on GTCs were detected and evaluated by MTT assay, AO/EB double staining, DNA fragmentation assay and flow cytometry analysis. Results showed that SW treatment significantly suppressed GTCs viability and induced typical apoptotic features in a time- and concentration-dependent manner. SW treatment increased Bax protein levels, reduced Bcl-2 protein levels, induced Bax translocation to mitochondria, and triggered the release of cytochrome c from mitochondria into cytosol, which in turn activated caspase-9 and caspase-3, and cleaved PARP, resulting in GTCs apoptosis. However, caspase-8 activity and the level of Bid did not exhibit significant changes in the process of SW-induced apoptosis. In addition, TUNEL assay suggested that SW induced GTCs apoptosis but not other cells in goat placenta cotyledons. Taken together, these data suggest that SW selectively induces GTCs apoptosis via the activation of mitochondria-mediated apoptosis pathway in goat placenta cotyledons, which might contribute to placentae impairment and abortion in pregnant goats fed with SW-containing plants. These findings may provide new insights to understand the mechanisms involved in SW-caused goat's abortion.