title: Elevated Expression of Carboxy-Terminal Modulator Protein (CTMP) Aggravates Brain Ischemic Injury in Diabetic db/db Mice.
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 affects the outcome of ischemia. Inhibitors specifically targeting CTMP may be beneficial in the treatment of cerebral ischemia in patients with diabetes.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.|Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.|Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Min
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.|Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.|Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.|Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Shiquan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.|Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. hldong6@hotmail.com.|Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. hldong6@hotmail.com.
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. mzkxlz@126.com.|Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. mzkxlz@126.com.
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D008822:Mice, Transgenic; D009025:Morpholines / Q000494:pharmacology; D010170:Palmitoyl-CoA Hydrolase; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D002867:Chromones; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; C527670:CTMP protein, mouse; D010170:Palmitoyl-CoA Hydrolase
keywords: Akt; CTMP; Cerebral ischemia; Diabetes mellitus; Endogenous inhibitor; db/db mice