PCV2 Triggers PK-15 Cell Apoptosis Through the PLC–IP3R–Ca2+ Signaling Pathway

Abstract

The endoplasmic reticulum (ER) plays an essential role in Ca2+ concentration balance and protein biosynthesis. During infection, the virus needs to complete its life process with the help of ER. At the same time, ER also produces ER stress (ERS), which induces apoptosis to resist virus infection. Our study explored the Ca2+ concentration, ERS, and the apoptosis mechanism after porcine circovirus 2 (PCV2) infection. We show here that PCV2 infection induces the increased cytoplasmic Ca2+ level and PK-15 cell ER swelling. The colocalization of phospholipase C (PLC) and inositol 1,4,5-trisphosphate receptor (IP3R) in the cytoplasm was observed by laser confocal microscopy. Western blot and quantitative polymerase chain reaction experiments confirmed that PLC and IP3R expression levels increased after PCV2 infection, and Ca2+ concentration in the cytoplasm increased after virus infection. These results suggest that PCV2 infection triggers ERS of PK-15 cells via the PLC–IP3R–Ca2+ signaling pathway to promote the release of intracellular Ca2+ and led to cell apoptosis.

Research progress of signaling pathways of the natural substances intervene dyslipidemia (Review)

“…In particular, APN and LEP are closely associated with lipid metabolism in the body (59). APN regulates lipid metabolism by activating the AMPK signaling pathway as previously described (32,33). LEP serves a key role in the process of lipid metabolism through a continuous process (Fig.…”

“…When the AMP/ATP ratio is increased, which indicates that the intracellular energy levels are low, liver kinase B1 translocates from the nucleus into the cytosol to activate AMPK by phosphorylation at Thr172 (31). Alternatively, AMPK can be activated by adiponectin (APN), which binds to its receptor to activate phospholipase C to convert phosphatidylinositol 4,5-bisphosphate (PIP 2 ) into inositol triphosphate (IP 3 ) (32). IP 3 then binds with the IP 3 receptor on the endoplasmic reticulum membrane to promote Ca 2+ release (32).…”

“…Alternatively, AMPK can be activated by adiponectin (APN), which binds to its receptor to activate phospholipase C to convert phosphatidylinositol 4,5-bisphosphate (PIP 2 ) into inositol triphosphate (IP 3 ) (32). IP 3 then binds with the IP 3 receptor on the endoplasmic reticulum membrane to promote Ca 2+ release (32). Ca 2+ then activates calmodulin-dependent protein kinase kinase, which in turn activates AMPK also by phosphorylation at the Thr172 residue (33).…”

Advances in Crosstalk between Porcine Circoviruses and Host

“…The ERS driven by PCV2 is Cap-dependent and may cause apoptosis by interfering with intracellular Ca 2+ homeostasis and ROS accumulation and activating the PERK pathway [ 102 , 103 , 104 ]. The decrease in Ca 2+ -ATP4 level in the cytoplasm may inhibit Ca 2+ efflux.…”

“…The decrease in Ca 2+ -ATP4 level in the cytoplasm may inhibit Ca 2+ efflux. At the same time, the increase in phospholipase C (PLC) and IP3R-1 may trigger Ca 2+ release from the ER to the cytoplasm, which contributes to the rise in Ca 2+ concentration ([Ca 2+ ]i) and the binding of [Ca 2+ ]i to calmodulin, leading to cell apoptosis [ 103 , 104 ]. In addition, a mitochondrial localization signal (MLS) was identified in the N-terminus of the PCV2 Cap (16–42 aa), which overlapped with the viral NLS (1–41 aa) [ 69 ].…”