p38 Inhibitor Protects Mitochondrial Dysfunction by Induction of DJ-1 Mitochondrial Translocation After Subarachnoid...

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• p38 mitogen-activated protein kinase (MAPK) is implicated in mitochondrial dysfunction following subarachnoid hemorrhage (SAH).
• DJ-1 protein responds to oxidative stress, translocates to mitochondria, and maintains mitochondrial homeostasis.
• The precise role of DJ-1 in p38-mediated mitochondrial dysfunction post-SAH remains unclear.

Purpose of the Study:

• To investigate the relationship between DJ-1 and p38 activation in mitochondrial dysfunction after SAH.
• To elucidate the mechanisms underlying p38-induced mitochondrial damage and autophagy alterations in an in vitro SAH model.

Main Methods:

• Utilized an in vitro subarachnoid hemorrhage (SAH) model.
• Assessed the expression of p38, phosphorylated p38 (p-p38), DJ-1, and autophagy-related proteins.
• Administered a p38 inhibitor to evaluate its effects on mitochondrial function and autophagy.

Main Results:

• p38 inhibitor suppressed excessive p38 and p-p38 expression post-SAH.
• Total and mitochondrial DJ-1 expression were upregulated following SAH.
• p38 inhibition ameliorated oxyhemoglobin (OxyHb)-induced mitochondrial dysfunction, including membrane potential loss and reactive oxygen species (ROS) release.
• p38 inhibition restored abnormal autophagic flux by modulating Atg5, beclin-1, LC3-II/LC3-I ratio, and p62.

Conclusions:

• Overexpression of p38 contributes to mitochondrial dysfunction and abnormal autophagy post-SAH.
• DJ-1 mitochondrial translocation plays a significant role in p38-induced mitochondrial damage.
• Targeting the p38 pathway may offer a therapeutic strategy for SAH-related mitochondrial injury.