Hyperglycemia aggravates decreases of PEA-15 and its two phosphorylated forms in cerebral ischemia

J Vet Med Sci. 2017 Mar 28;79(3):654-660. doi: 10.1292/jvms.16-0437. Epub 2017 Feb 17.

Abstract

Diabetes is a metabolic health disorder and an important risk factor for stroke. Phosphoprotein enriched in astrocytes 15 (PEA-15) is a multifunctional protein modulating cell proliferation, survival, apoptosis and glucose metabolism. This study investigated whether diabetes modulates the expression of PEA-15 and two phosphorylated forms (Ser 104 and Ser 116) in middle cerebral artery occlusion (MCAO)-induced brain injury. Male Sprague-Dawley rats were administrated with streptozotocin (40 mg/kg) and were underwent right middle cerebral artery occlusion (MCAO) 4 weeks after streptozotocin injection. Brain tissues were collected 24 hr after MCAO and stained using triphenyltetrazolium chloride. Western blot analysis was performed to elucidate the expression of PEA-15 and two phosphorylated forms (Ser 104 and Ser 116) in right cerebral cortex. Infarct volume during MCAO injury was severely increased in diabetic animals compared to non-diabetic animals. We identified the decrease in PEA-15 in animals that underwent MCAO using proteomic approach. PEA-15 expression during MCAO was strongly decreased in diabetic animals compared to non-diabetic animals. Western blots analysis confirmed that diabetes exacerbated the decrease in PEA-15 expression after MCAO. Moreover, decrease in expression of phospho-PEA-15 (Ser 104 and Ser 116) was greater in diabetic than in non-diabetic animals. These results suggested that a diabetic condition may aggravate brain damage through decreasing expression of PEA-15 and phospho-PEA-15 (Ser 104 and Ser 116) in ischemic brain injury.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Brain Ischemia / etiology*
  • Brain Ischemia / metabolism
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Neuropathies / etiology*
  • Diabetic Neuropathies / metabolism
  • Hyperglycemia / complications*
  • Hyperglycemia / metabolism
  • Male
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Serine / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Pea15 protein, rat
  • Phosphoproteins
  • Serine