The expression regulation and protective role of Pnn in neural cells exposed to ischemic stress

抄録

Background: Pnn, a multifunctional protein, participates in embryogenesis as well as in apoptosis, proliferation, and metastasis in tumor cells through regulating gene transcription and mRNA alternative splicing. However, the role of Pnn in non-dividing cells, particularly regarding stress response in neural cells, remains unknown.

Methods: In the present study, we applied oxygen-glucose deprivation (OGD) -treated primary cultured rat neural cells and mice with middle cerebral artery occlusion (MCAO)-induced ischemic stroke to examine the alternation of Pnn in the stress response to ischemic insults. Cells and mouse models with Pnn depletion were also used to examine its role in response to ischemic stress.

Results: The expression level of Pnn was increased immediately after exposure to oxygen-glucose deprivation (OGD) and then declined in the reoxygenation period. Moreover, the nuclear speckle Pnn was gradually translocated to the cytosol during the reoxygenation period in a time-dependent manner. The apoptosis-associated proteins in the primary cortical neurons were also found to be increased with OGD/reoxygenation. In primary astrocytes, Pnn is localized mostly in the nuclear speckle both under the normoxia and the OGD condition. Unlike that in neurons, the Pnn expression in astrocytes was decreased immediately after OGD and then gradually up-regulated during the reoxygenation period. Three-days post induction of ischemic stroke in mice, the neuronal expression of Pnn in the peri-ischemic region was reduced. However, the Pnn expression in astrocytes was not altered. Moreover, the nuclear speckle distribution of Pnn in neurons was also diminished following ischemic stroke. In both cell and mouse models with gene manipulation, reduced expression of Pnn results in poor survival rate and prognosis to ischemic stresses.

Conclusions: the Pnn expression regulation after OGD and during reoxygenation shows distinct manner in neurons and astrocytes, while the expression level of Pnn modulates the stress response to ischemic injury in neural cells.