scholarly journals RIPK3-Dependent Necroptosis Limits PRV Replication in PK-15 Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongchao Gou ◽  
Zhibiao Bian ◽  
Rujian Cai ◽  
Pinpin Chu ◽  
Shuai Song ◽  
...  
Keyword(s):  
Cell Death ◽  
Pseudorabies Virus ◽  
Specific Inhibitor ◽  
Host Cells ◽  
Positive Staining ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Transmission Electron Microscopy Analysis ◽  
Necrosis Factor Alpha ◽  
Infected Cells

Pigs infected by pseudorabies virus (PRV) display necrotic pathology in multiple organs. The mechanism by which PRV induces cell death is still unclear. Recently, necroptosis was identified as a programmed process dependent on the receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase-like protein (MLKL). In this study, we demonstrated that PRV induced RIPK3-dependent necroptosis in PK-15 cells. The data showed that PRV infection caused cell death with Propidium Iodide (PI)-positive staining. Transmission electron microscopy analysis indicated plasma membrane disruption in PRV-infected cells. A pan-caspase inhibitor did not prevent PRV-induced necrotic cell death. Western blot analysis indicated that caspase-3 and caspase-8 were not cleaved during PRV infection. Although the transcription of tumor necrosis factor-alpha (TNF-α) was increased by PRV infection, RIPK1 was shown to be not involved in PRV-induced necrotic cell death by use of its specific inhibitor. Further experiments indicated that the phosphorylation of RIPK3 and MLKL was upregulated in PRV-infected cells. Stable shRNA knockdown of RIPK3 or MLKL had a recovery effect on PRV-induced necrotic cell death. Meanwhile, viral titers were enhanced in RIPK3 and MLKL knockdown cells. Hence, we concluded that initiation of necroptosis in host cells plays a limiting role in PRV infection. Considering that necroptosis is an inflammatory form of programmed cell death, our data may be beneficial for understanding the necrotic pathology of pigs infected by PRV.

Lysozyme facilitates adherence of Enterococcus faecium to host cells and induction of necrotic cell death

2012 ◽  
Vol 14 (6) ◽  
pp. 554-562 ◽  
Author(s):  
Steffen Höring ◽  
Monika Schütz ◽  
Ingo B. Autenrieth ◽  
Sabine Gröbner
Keyword(s):  
Cell Death ◽  
Enterococcus Faecium ◽  
Host Cells ◽  
Necrotic Cell Death ◽  
Necrotic Cell

scholarly journals Involvement of Caspase-9 in the Inhibition of Necrosis of RAW 264 Cells Infected with Mycobacterium tuberculosis

2007 ◽  
Vol 75 (6) ◽  
pp. 2894-2902 ◽  
Author(s):  
Ryosuke Uchiyama ◽  
Ikuo Kawamura ◽  
Takao Fujimura ◽  
Michiko Kawanishi ◽  
Kohsuke Tsuchiya ◽  
...  
Keyword(s):  
Cell Death ◽  
Mycobacterium Tuberculosis ◽  
Host Cell ◽  
Specific Inhibitor ◽  
Host Cells ◽  
Ros Generation ◽  
Caspase 9 ◽  
Host Cell Death ◽  
Intracellular Ros ◽  
Infected Cells

ABSTRACT In order to know how caspases contribute to the intracellular fate of Mycobacterium tuberculosis and host cell death in the infected macrophages, we examined the effect of benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethane (z-VAD-fmk), a broad-spectrum caspase inhibitor, on the growth of M. tuberculosis H37Rv in RAW 264 cells. In the cells treated with z-VAD-fmk, activation of caspase-8, caspase-3/7, and caspase-9 was clearly suppressed, and DNA fragmentation of the infected cells was also reduced. Under this experimental condition, it was found that the treatment markedly inhibited bacterial growth inside macrophages. The infected cells appeared to undergo cell death of the necrosis type in the presence of z-VAD-fmk. We further found that z-VAD-fmk treatment resulted in the generation of intracellular reactive oxygen species (ROS) in the infected cells. By addition of a scavenger of ROS, the host cell necrosis was inhibited and the intracellular growth of H37Rv was significantly restored. Among inhibitors specific for each caspase, only the caspase-9-specific inhibitor enhanced the generation of ROS and induced necrosis of the infected cells. Furthermore, we found that severe necrosis was induced by infection with H37Rv but not H37Ra in the presence of z-VAD-fmk. Caspase-9 activation was also detected in H37Rv-infected cells, but H37Ra never induced such caspase-9 activation. These results indicated that caspase-9, which was activated by infection with virulent M. tuberculosis, contributed to the inhibition of necrosis of the infected host cells, presumably through suppression of intracellular ROS generation.

Oleanolic acid rich solubilized triterpene extracts from mistletoe induce apoptotic and necrotic cell death of murine B16. F10 melanoma cells

Planta Medica ◽  
2009 ◽  
Vol 75 (09) ◽  
Author(s):  
CM Strüh ◽  
S Jäger ◽  
CM Schempp ◽  
T Jakob ◽  
A Scheffler ◽  
...  
Keyword(s):  
Cell Death ◽  
Oleanolic Acid ◽  
Melanoma Cells ◽  
Necrotic Cell Death ◽  
Necrotic Cell

NADPH Oxidases: New Players in TNF-Induced Necrotic Cell Death

2007 ◽  
Vol 26 (6) ◽  
pp. 769-771 ◽  
Author(s):  
Tom Vanden Berghe ◽  
Wim Declercq ◽  
Peter Vandenabeele
Keyword(s):  
Cell Death ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Nadph Oxidases

BNip3 is a mediator of TNF-induced necrotic cell death

APOPTOSIS ◽  
2010 ◽  
Vol 16 (2) ◽  
pp. 114-126 ◽  
Author(s):  
Jee-Youn Kim ◽  
Yong-Jun Kim ◽  
Sun Lee ◽  
Jae-Hoon Park
Keyword(s):  
Cell Death ◽  
Necrotic Cell Death ◽  
Necrotic Cell

scholarly journals Protein synthesis persists during necrotic cell death

2005 ◽  
Vol 168 (4) ◽  
pp. 545-551 ◽  
Author(s):  
Xavier Saelens ◽  
Nele Festjens ◽  
Eef Parthoens ◽  
Isabel Vanoverberghe ◽  
Michael Kalai ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Synthesis ◽  
De Novo ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Proteolytic Activation ◽  
Double Stranded Rna ◽  
Molecular Events

Cell death is an intrinsic part of metazoan development and mammalian immune regulation. Whereas the molecular events orchestrating apoptosis have been characterized extensively, little is known about the biochemistry of necrotic cell death. Here, we show that, in contrast to apoptosis, the induction of necrosis does not lead to the shut down of protein synthesis. The rapid drop in protein synthesis observed in apoptosis correlates with caspase-dependent breakdown of eukaryotic translation initiation factor (eIF) 4G, activation of the double-stranded RNA-activated protein kinase PKR, and phosphorylation of its substrate eIF2-α. In necrosis induced by tumor necrosis factor, double-stranded RNA, or viral infection, de novo protein synthesis persists and 28S ribosomal RNA fragmentation, eIF2-α phosphorylation, and proteolytic activation of PKR are absent. Collectively, these results show that, in contrast to apoptotic cells, necrotic dying cells retain the opportunity to synthesize proteins.

Sign in / Sign up

Export Citation Format

Share Document