Induction of Autophagy with rapamycin overcomes Bcl‐2's deleterious effects on stroke outcome

• Published in: The FASEB journal 2013-04, Vol.27 (S1)
• Main Authors: Buckley, Kathleen Mary, Hoda, Nasrul, Herberg, Samuel, Barrett, John R, Periyasamy‐Thandavan, Sudharsan, Kondrikova, Galina, Hess, Daniel L, Hess, David C, Schoenlein, Patricia V, Hill, William D
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.27.1_supplement.lb514

Abstract only Only one therapy is currently approved to treated ischemic strokes and the majority of patients do not have an opportunity to receive treatment, indicating a need for further treatment areas. One area that has been attractive is to target delayed cell death pathways in the penumbra. An emerging stroke literature indicates that in addition to apoptotic cell death, autophagy is seen after stroke. Autophagy is a process of regulated turnover of cellular constituents through an autophagosomal‐lysosomal pathway and plays a key role in cell homeostasis, development, normal growth control and during bioenergetic stress. At a crossroad between apoptosis and autophagy is the anti‐apoptotic protein Bcl‐2, which acts to block apoptosis by preventing mitochondrial leakage, but it is also anti‐autophagy as it binds the protein Beclin‐1 and prevents initiation of autophagy. The balance of Bcl‐2 activity after stroke and its effect on stroke outcome are not well understood. We show that normal basal autophagy is higher in brain than any other tissue and levels of Bcl‐2 are low in the brain. We demonstrate that autophagy is up‐regulated in the brain and that stroke injury increases expression of the anti‐apoptotic and anti‐autophagy protein, Bcl‐2. Treatment with rapamycin can help to overcome the Bcl‐2 initiated blockade of autophagy and improve stroke outcome.