PKM2 Involved in Neuronal Apoptosis on Hypoxic-ischemic Encephalopathy in Neonatal Rats

Area of Science:

• Neuroscience
• Biochemistry
• Cell Biology

Background:

• Pyruvate Kinase isozymes M2 (PKM2) is a key glycolytic enzyme.
• PKM2 is known to influence tumor growth, cell division, angiogenesis, apoptosis, and metastasis.
• Its role in neuronal injury, particularly after hypoxic-ischemic encephalopathy (HIE), remains less understood.

Purpose of the Study:

• To investigate the role of PKM2 in cortical neurons following HIE in newborn rats.
• To elucidate the molecular mechanisms underlying PKM2's involvement in neuronal apoptosis.

Main Methods:

• Immunohistochemistry and Western blot analysis were used to assess PKM2 protein expression.
• Double immunofluorescence labeling identified PKM2 localization in cortical neurons.
• TUNEL staining and siRNA-mediated silencing were employed to evaluate PKM2's role in apoptosis and its effect on AKT phosphorylation.

Main Results:

• PKM2 protein expression peaked at 24 hours post-HIE in the ipsilateral cerebral cortex.
• PKM2 was primarily localized in neurons, with increased active caspase-3 and decreased phosphorylated AKT (p-AKT) levels observed.
• Silencing PKM2 reduced active caspase-3 and upregulated p-AKT expression, suggesting PKM2 mediates apoptosis via p-AKT inactivation.

Conclusions:

• PKM2 is upregulated in cortical neurons following HIE.
• PKM2 appears to promote neuronal apoptosis after HIE, potentially through the inactivation of the AKT signaling pathway.
• Targeting PKM2 may offer a therapeutic strategy for HIE-induced brain injury.