Elevated Expression of Carboxy-Terminal Modulator Protein (CTMP) Aggravates Brain Ischemic Injury in Diabetic db/db Mice.

Elevated Expression of Carboxy-Terminal Modulator Protein (CTMP) Aggravates Brain Ischemic Injury in Diabetic db/db Mice.
Neurochem Res. 2016 May 9;
Authors: Chen Y, Cai M, Deng J, Tian L, Wang S, Tong L, Dong H, Xiong L
Abstract
Deregulation of Akt signaling is important in the brain injuries caused by cerebral ischemia in diabetic animals, and the underlying mechanism is not fully understood. We investigated the role of carboxy-terminal modulator protein (CTMP), an endogenous Akt inhibitor, in brain injury following focal cerebral ischemia in type 2 diabetic db/db mice and their control littermates non-diabetic db/+ mice. db/db mice showed a significant elevation in the expression of CTMP compared to db/+ mice under normal physiological conditions. After ischemia, db/db mice exhibit higher levels of CTMP expression, decreased Akt kinase activity, adverse neurological deficits and cerebral infarction than db/+ mice. To further certain the effectiveness of Akt signaling to the final outcome of cerebral ischemia, the animals were treated with LY294002, an inhibitor of the Akt pathway, which aggravated the ischemic injury in db/+ mice but not in db/db mice. RNA interference-mediated depletion of CTMP were finally applied in db/db mice, which restored Akt activity, improved neurological scores and reduced infarct volume. These results suggest that elevation of CTMP in diabetic mice suppresses Akt activity and ultimately negatively affec...

Source: Neurochemical Research - May 8, 2016 Category: Neuroscience Authors: Chen Y, Cai M, Deng J, Tian L, Wang S, Tong L, Dong H, Xiong L Tags: Neurochem Res Source Type: research