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SC79, the AKT Activator Protects Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury.
Med Sci Monit. 2018 Aug 03; 24:5391-5397.MS

Abstract

BACKGROUND

Activation of AKT pathway attenuates brain damage and neuronal apoptosis during cerebral ischemia/reperfusion (I/R) injury. SC79 is a novel, selective and highly-efficient Akt activator. This study aimed to investigate the neuroprotective effect of SC79 against cerebral I/R injury in a rat model, and to explore the possible underlying mechanisms. MATERIAL AND

METHODS

Male Sprague-Dawley rats received cerebral ischemia for 1 hour, followed by brain reperfusion for 0.5-24 hours. The cerebral I/R injury animal model were treated with SC79 alone or SC79 in combination with LY294002. Western blots were used to detect the levels of expression of phosphatidylinositol AKT (p-Akt), Bax, and bcl-2. Twenty-four hours after cerebral I/R, the degree of brain injury was evaluated by detecting the neurological deficit score (NDS). The infarct rate of brain tissue was observed by TTC (2, 3, 5-triphenyltetrazolium chloride) staining. TUNEL (terminal deoxynucleotidyl transferase-mediated UTP nick end labeling) staining was used to detect cell apoptosis.

RESULTS

p-Akt was activated during early cerebral I/R at 0.5 hours, and reached the highest levels at 4 hours, then gradually decreased from 6 hours, and reached and maintained the lowest levels at 12-24 hours. Bax expression was gradually increased from 6 hours and reached the highest level at 24 hours. However, bcl-2 expression was gradually increased and reached the highest levels at 4 hours, then gradually decreased from 6 hours, and reached the lowest levels at 24 hours. Administration of SC79 decreased infarct volumes and improved neurological function significantly. LY294002 in combination with SC79 lost the capability of SC79 to resist the cerebral I/R injury. SC79 treatment alone activated p-Akt and promoted anti-apoptotic bcl-2 and inhibited anti-apoptotic Bax expression in middle cerebral artery occlusion (MCAO) mice. However, combined SC79 and LY294002 treatment abolished SC79-induced p-Akt activity, inhibited anti-apoptotic bcl-2 and promoted anti-apoptotic Bax expression in MCAO mice. Furthermore, SC79 treatment alone attenuated apoptotic neuronal cell death, but abolished this effect in SC79 in combination with LY294002 treated groups.

CONCLUSIONS

SC79 significantly increased Akt activation and reduced infarct volume and subsequently improved neurological function in ischemic brain after cerebral I/R injury in rats. These findings suggested that SC79 may be as a neuroprotective drug to be potentially used in the clinic.

Authors+Show Affiliations

Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).Department of Emergency, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).Department of Emergency, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China (mainland).

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30074018

Citation

Luan, Qi, et al. "SC79, the AKT Activator Protects Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury." Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, vol. 24, 2018, pp. 5391-5397.
Luan Q, Pan L, He D, et al. SC79, the AKT Activator Protects Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury. Med Sci Monit. 2018;24:5391-5397.
Luan, Q., Pan, L., He, D., Gong, X., & Zhou, H. (2018). SC79, the AKT Activator Protects Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 24, 5391-5397. https://doi.org/10.12659/MSM.910191
Luan Q, et al. SC79, the AKT Activator Protects Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury. Med Sci Monit. 2018 Aug 3;24:5391-5397. PubMed PMID: 30074018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SC79, the AKT Activator Protects Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury. AU - Luan,Qi, AU - Pan,Lixiao, AU - He,Dongyong, AU - Gong,Xingji, AU - Zhou,Hui, Y1 - 2018/08/03/ PY - 2018/8/4/entrez PY - 2018/8/4/pubmed PY - 2018/11/6/medline SP - 5391 EP - 5397 JF - Medical science monitor : international medical journal of experimental and clinical research JO - Med. Sci. Monit. VL - 24 N2 - BACKGROUND Activation of AKT pathway attenuates brain damage and neuronal apoptosis during cerebral ischemia/reperfusion (I/R) injury. SC79 is a novel, selective and highly-efficient Akt activator. This study aimed to investigate the neuroprotective effect of SC79 against cerebral I/R injury in a rat model, and to explore the possible underlying mechanisms. MATERIAL AND METHODS Male Sprague-Dawley rats received cerebral ischemia for 1 hour, followed by brain reperfusion for 0.5-24 hours. The cerebral I/R injury animal model were treated with SC79 alone or SC79 in combination with LY294002. Western blots were used to detect the levels of expression of phosphatidylinositol AKT (p-Akt), Bax, and bcl-2. Twenty-four hours after cerebral I/R, the degree of brain injury was evaluated by detecting the neurological deficit score (NDS). The infarct rate of brain tissue was observed by TTC (2, 3, 5-triphenyltetrazolium chloride) staining. TUNEL (terminal deoxynucleotidyl transferase-mediated UTP nick end labeling) staining was used to detect cell apoptosis. RESULTS p-Akt was activated during early cerebral I/R at 0.5 hours, and reached the highest levels at 4 hours, then gradually decreased from 6 hours, and reached and maintained the lowest levels at 12-24 hours. Bax expression was gradually increased from 6 hours and reached the highest level at 24 hours. However, bcl-2 expression was gradually increased and reached the highest levels at 4 hours, then gradually decreased from 6 hours, and reached the lowest levels at 24 hours. Administration of SC79 decreased infarct volumes and improved neurological function significantly. LY294002 in combination with SC79 lost the capability of SC79 to resist the cerebral I/R injury. SC79 treatment alone activated p-Akt and promoted anti-apoptotic bcl-2 and inhibited anti-apoptotic Bax expression in middle cerebral artery occlusion (MCAO) mice. However, combined SC79 and LY294002 treatment abolished SC79-induced p-Akt activity, inhibited anti-apoptotic bcl-2 and promoted anti-apoptotic Bax expression in MCAO mice. Furthermore, SC79 treatment alone attenuated apoptotic neuronal cell death, but abolished this effect in SC79 in combination with LY294002 treated groups. CONCLUSIONS SC79 significantly increased Akt activation and reduced infarct volume and subsequently improved neurological function in ischemic brain after cerebral I/R injury in rats. These findings suggested that SC79 may be as a neuroprotective drug to be potentially used in the clinic. SN - 1643-3750 UR - https://www.unboundmedicine.com/medline/citation/30074018/SC79_the_AKT_Activator_Protects_Cerebral_Ischemia_in_a_Rat_Model_of_Ischemia/Reperfusion_Injury_ L2 - https://www.medscimonit.com/download/index/idArt/910191 DB - PRIME DP - Unbound Medicine ER -