NOVEL MECHANISMS FOR PROTEIN SYNTHESIS REGULATION DURING STRESS

Protein synthesis is important for living organisms to overcome the environmental stresses, such as nutrient deprivation and disease. Although many animal and human studies have reported changes in protein synthesis rates under various conditions, little is known about the mechanism that regulate protein synthesis in different tissues and during diseases, such as diabetes. To better understand the regulation of protein synthesis during nutrient deprivation, we have measured protein synthesis rates in rats that were fasted or were calorie restricted. We found that protein synthesis rates were regulated differently in rat tissues when nutrients were limited. In cardiac muscle protein synthesis rates did not change under these conditions. After 24 hours of fasting, relatively smaller changes in protein synthesis were seen in the heart. Currently not much is known about the rate and regulation of protein synthesis in the isolated pancreatic islets and ¿¿-cells. To measure protein synthesis in the pancreatic islets, we have developed a novel experimental technique by combining the islet isolation technique and deuterium water labeling method. The Akita mouse, which bears a point mutation on INS2 gene, was chosen for this study because the onset of diabetes does not involve obesity, insulin resistance or pancreatitis. In themouse we found that protein synthesis in pancreatic islets was positively correlated with chronic endoplasmic reticulum (ER) stress. The increase in protein synthesis in the islets of Akita mice was associated with an increase in expression of some ER stress-related genes (such as Activating transcription factor, ATF4, and CHOP) similar to the response observed under nutrient deprivation. To analyze the consequence of acute stress in the ER we studied the rate of protein synthesis after 24 or 48 hours of tunicamycin-induced ER stress, as compared to chronic ER stress, observed in the islets from Akita mice. We found that acute transient stress caused a decrease in protein synthesis in pancreatic islets compared to that in chronic ER stress. Therefore we conclude that the regulation of protein synthesis responds to stresses in a tissue specific and developmental manner.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Nutrition

Grantor dc:publisher

Case Western Reserve University School of Graduate Studies

Year dc:date

2013

Author dc:creator

• Yuan, Celvie Lim

Contributors dc:contributor

• Manor, Danny
• Maria, Hatzoglou

• Biochemistry
• Nutrition

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=case1355803614

OAI identifier oai:identifier

oai:etd.ohiolink.edu:case1355803614