Identification of proteins in hyperglycemia and stroke animal models

• Published in: The Journal of surgical research Vol. 200; no. 1; pp. 365 - 373
• Main Authors: Sung, Jin-Hee, PhD, Shah, Fawad-Ali, MS, Gim, Sang-Ah, DVM, MS, Koh, Phil-Ok, DVM, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2016
• Subjects: Animals; Biomarkers - metabolism; Brain Ischemia - complications; Brain Ischemia - metabolism; Cerebral Cortex - metabolism; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - metabolism; Electrophoresis, Gel, Two-Dimensional; Hyperglycemia; Hyperglycemia - complications; Hyperglycemia - metabolism; Male; Mass Spectrometry; Proteome - metabolism; Proteomics; Random Allocation; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Streptozocin; Streptozotocin; Stroke; Stroke - complications; Stroke - metabolism; Surgery; Hyperglycemia; Stroke; Streptozotocin; Proteomics
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2015.07.020

Abstract Background Stroke is a major cause of disability and death in adults. Diabetes mellitus is a metabolic disorder that strongly increases the risk of severe vascular diseases. This study compared changes in proteins of the cerebral cortex during ischemic brain injury between nondiabetic and diabetic animals. Methods Adult male rats were injected with streptozotocin (40 mg/kg) via the intraperitoneal route to induce diabetes and underwent surgical middle cerebral artery occlusion (MCAO) 4 wk after streptozotocin treatment. Cerebral cortex tissues were collected 24 h after MCAO and cerebral cortex proteins were analyzed by two-dimensional gel electrophoresis and mass spectrometry. Results Several proteins were identified as differentially expressed between nondiabetic and diabetic animals. Among the identified proteins, we focused on the following metabolism-related enzymes: isocitrate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, adenosylhomocysteinase, pyruvate kinase, and glucose-6-phosphate isomerase (neuroleukin). Expression of these proteins was decreased in animals that underwent MCAO. Moreover, protein expression was reduced to a greater extent in diabetic animals than in nondiabetic animals. Reverse transcription–polymerase chain reaction analysis confirmed that the diabetic condition exacerbates the decrease in expression of metabolism-related proteins after MCAO. Conclusions These results suggest that the diabetic condition may exacerbate brain damage during focal cerebral ischemia through the downregulation of metabolism-related proteins.