DND
Visiting Speaker – Dr. Subrata Chakrabarti
Posted on: May 15, 2012
Friday, May 18th, 2012
12:00 Noon - Samuel Cohen Auditorium
St. Boniface Hospital Research (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-ęB 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