Lab Anim Res.  2013 Jun;29(2):63-69. 10.5625/lar.2013.29.2.63.

Ferulic acid regulates the AKT/GSK-3beta/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model

• Gim SA
• Sung JH
• Shah FA
• Kim MO
• Koh PO

• KMID: 1431333
• DOI: http://doi.org/10.5625/lar.2013.29.2.63

Abstract

Ferulic acid, a component of the plants Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort, exerts a neuroprotective effect by regulating various signaling pathways. This study showed that ferulic acid treatment prevents the injury-induced increase of collapsin response mediator protein 2 (CRMP-2) in focal cerebral ischemia. Glycogen synthase kinase-3beta (GSK-3beta) regulates CRMP-2 function through phosphorylation of CRMP-2. Moreover, the pro-apoptotic activity of GSK-3beta is inactivated by phosphorylation by Akt. This study investigated whether ferulic acid modulates the expression of CRMP-2 and its upstream targets, Akt and GSK-3beta, in focal cerebral ischemia. Male rats were treated immediately with ferulic acid (100 mg/kg, i.v.) or vehicle after middle cerebral artery occlusion (MCAO), and then cerebral cortices were collected 24 hr after MCAO. MCAO resulted in decreased levels of phospho-Akt and phospho-GSK-3beta, while ferulic acid treatment prevented the decrease in the levels of these proteins. Moreover, phospho-CRMP-2 and CRMP-2 levels increased during MCAO, whereas ferulic acid attenuated these injury-induced increases. These results demonstrate that ferulic acid regulates the Akt/GSK-3beta/CRMP-2 signaling pathway in focal cerebral ischemic injury, thereby protecting against brain injury.

Keyword

Ferulic acid; neuroprotection; Akt; GSK-3beta; CRMP-2

MeSH Terms

Angelica sinensis
Animals
Brain Injuries
Brain Ischemia
Cerebral Cortex
Coumaric Acids
Glycogen Synthase
Glycogen Synthase Kinase 3
Humans
Infarction, Middle Cerebral Artery
Ligusticum
Male
Middle Cerebral Artery
Neuroprotective Agents
Phosphorylation
Proteins
Rats
Semaphorin-3A
Coumaric Acids
Glycogen Synthase
Glycogen Synthase Kinase 3
Neuroprotective Agents
Proteins
Semaphorin-3A

Figure

• 

  Figure 1 Collapsin response mediator protein 2 (CRMP-2) protein spots identified by MALDI-TOF in the cerebral cortex from vehicle+middle cerebral artery occlusion (MCAO), ferulic acid+MCAO, vehicle+sham, ferulic acid+sham animals. Circles indicate the CRMP-2 protein spots. The intensity of spots was measured using PDQuest software. The ratio of intensity is described as spots intensity of these animals to spots intensity of sham+vehicle animals. Data (n=5) are shown as mean±SEM. *P<0.05. Mw and IP indicate molecular weight and isoelectrical point, respectively.

• 

  Figure 2 Western blot analysis of phospho-Akt and Akt in the cerebral cortex from vehicle+middle cerebral artery occlusion (MCAO), ferulic acid+MCAO, vehicle+sham, ferulic acid+sham animals. Each lane represents an individual experimental animal. Densitometric analysis is represented as these proteins intensity to β-actin intensity. Molecular weight (kDa) is depicted at right. Data (n=5) are represented as mean±SEM. *P<0.05.

• 

  Figure 3 Western blot analysis of phospho-GSK-3β and GSK-3β in the cerebral cortex from vehicle + middle cerebral artery occlusion (MCAO), ferulic acid+MCAO, vehicle+sham, ferulic acid+sham animals. Each lane represents an individual experimental animal. Densitometric analysis is represented as these proteins intensity to β-actin intensity. Molecular weight (kDa) is depicted at right. Data (n=5) are represented as mean±SEM. *P<0.05.

• 

  Figure 4 Western blot analysis of phospho-CRMP-2 and CRMP-2 in the cerebral cortex from vehicle+middle cerebral artery occlusion (MCAO), ferulic acid+MCAO, vehicle+sham, ferulic acid+sham animals. Each lane represents an individual experimental animal. Densitometric analysis is represented as these proteins intensity to β-actin intensity. Molecular weight (kDa) is depicted at right. Data (n=5) are represented as mean±SEM. *P<0.05.

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