Protective effects of isorhamnetin on N2a cell against endoplasmic reticulum stress-induced injury is mediated by PKCε

- Isorhamnetin attenuates TG-induced endoplasmic reticulum stress injury in N2a cells.
- Isorhamnetin protects N2a cells from ERS injury by inhibiting cytosolic Ca2+ overload and ROS production.
- The mechanism of Isorhamnetin against endoplasmic reticulum stress injury rely on PKCε phosphorylation.

Endoplasmic reticulum stress (ERS)-induced intracellular calcium (Ca2+) overload and ROS burst plays a critical role in apoptosis. Protein kinase C epsilon (PKCε) is involved in regulating the homeostasis of Ca2+ and ROS production. isorhamnetin (Iso), as an ROS scavenger, effectively inhibit apoptosis, but the mechanism is still unclear. This study was to investigate whether Iso can inhibit ERS-induced apoptosis in N2a cells, and the protective effects are involved in PKCε-mediated Ca2+ homeostasis and inhibition of ROS. The effects of Iso against ERS injury in N2a cells were detected by cell viability, the levels of Ca2+, apoptosis and reactive oxygen species (ROS). The protein GRP78 expression levels were measured by western blot assay. The results showed that Iso can reduce ERS-induced injury by inhibiting Ca2+ overload, reducing the generation of ROS and decreasing apoptosis. In addition, Iso can promote PKCε phosphorylation, and εV1-2 (a PKCε inhibitor) drastically attenuated the protective effects of Iso against ERS injury in N2a cells. In conclusion, we firstly demonstrated that Iso can elicit protective effects against ERS injury in N2a cells and these effects are mediated at least in part via PKCε pathway.

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