Neuroscience Seminar Series
Hosted by the Division of Neurodegenerative Disorders
Friday, May 18th, 2012
Samuel Cohen Auditorium St. Boniface Hospital Research
12:00 Noon (Video-linked to Bannatyne Campus, A229 Chown Bldg.)
Dr. Subrata Chakrabarti
Dept. of Pathology, Schulich School of Medicine and Dentistry, Western University and London Health Sciences Center, London, Ontario
Topic: Novel mechanisms in the pathogenesis of diabetic retinopathy.
Dysfunction of endothelial cell (ECs) causing increased production of vasoactive factors and extracellular matrix (ECM) proteins are characteristic features of chronic diabetic complications such as diabetic retinopathy. Glucose-induced biochemical alterations in the ECs activate a cascade of signaling pathways leading to such changes.
Chronic diabetes leads to the activation of a number of signaling proteins including protein kinase C and advanced glycation end product formation. These signaling cascades are activated in response to hyperglycemia-induced oxidative stress. Such aberrant signaling leads to activation of transcription factors, such as nuclear factor-κB and activating protein-1. Although transcription factors are of importance in the regulation of protein production, they remain ineffective without transcriptional co-activators. In diabetes, transcriptional co-activator p300, with histone acetyl transferase activity, regulates several transcription factors. In addition, microRNA alterations regulate gene expression and the downstream effects eg. increased vasoactive factor and ECM protein production. Blockers of oxidative stress and histone acetylation as well as selected miRNA mimics prevent such alteration.
Hence a complex web of pathways including intracellular signaling, epigenetics and miRNA alterations are involved in the pathogenesis of functional and structural changes in chronic diabetic complications. We have identified specific changes in the ECs and in the organs affected by diabetic complications such as retina. We have also identified novel adjunct treatment strategies, targeting epigenetic and transcriptional machinery for chronic diabetic complications such as retinopathy.
(Supported by Grants from Canadian Institute of health Research, Canadian Diabetes Association and Heart and Stroke Foundation of Ontario)
For more information contact DND Office: (T) 235.3939 or (E) dnd@sbrc.ca
Kelly Jorundson Administrative Manager Division of Neurodegenerative Disorders St. Boniface Hospital Research Department of Pharmacology & Therapeutics University of Manitoba
Tel: 204.235.3939 Fax: 204.237.4092 Email: kjorund@sbrc.ca OR kjorund@yahoo.ca Website: www.sbrc.ca/dnd OR www.umanitoba.ca/medicine/units/pharmacology