Protective Effects of ShcA Protein Silencing for Photothrombotic Cerebral Infarction
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ORIGINAL ARTICLE
Protective Effects of ShcA Protein Silencing for Photothrombotic Cerebral Infarction Jeong-Ah Hwang 1,2,3 & Nara Shin 1,2 & Hyo Jung Shin 1,2 & Yuhua Yin 1,2 & Hyeok Hee Kwon 1,2 & Hyewon Park 1,2 & Juhee Shin 1,2 & Song I Kim 1,2 & Dong Woon Kim 1,2 & Hee-Jung Song 4 Received: 17 May 2020 / Revised: 3 November 2020 / Accepted: 5 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Reactive oxygen species (ROS) exacerbate stroke-induced cell damage. We found that ShcA, a protein that regulates ROS, is highly expressed in a Rose Bengal photothrombosis model. We investigated whether ShcA is essential for mitophagy in ROS-induced cellular damage and determined whether ROS exacerbate mitochondrial dysfunction via ShcA protein expression. Ischemic stroke was generated by Rose Bengal photothrombosis in mice. To silence ShcA protein expression in the mouse brain, ShcA-targeting siRNA-encapsulated nanoparticles were intrathecally injected into the cisterna magna. Upon staining with antibodies against ShcA counterpart caspase-3 or NeuN, we found that the ShcA protein expression was increased in apoptotic neurons. In addition, mitochondrial dysfunction and excessive mitophagy were evident in photothrombotic stroke tissue. Infarct volumes were significantly reduced, and neurological deficits were diminished in the ShcA siRNA nanoparticle-treated group, compared with the negative control siRNA nanoparticletreated group. We confirmed that the reduction of ShcA expression by nanoparticle treatment rescued the expression of genes, associated with mitochondrial dynamics and mitophagy mediation in a stroke model. This study suggests that the regulation of ShcA protein expression can be a therapeutic target for reducing brain damage with mitochondrial dysfunction caused by thrombotic infarction. Keywords ShcA protein . Rose Bengal photothrombosis . Reactive oxygen species . Mitochondrial dysfunctions . Stroke
* Dong Woon Kim [email protected]
Juhee Shin [email protected]
* Hee-Jung Song [email protected]
Song I Kim [email protected]
Jeong-Ah Hwang [email protected] 1
Department of Medical Science, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea
2
Department of Anatomy and Cell Biology, Brain Research Institute, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea
3
Brain Korea 21 PLUS Project for Medical Science, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea
4
Department of Neurology, Chungnam National University College of Medicine and Sejong Hospital, Sejong 30099, Republic of Korea
Nara Shin [email protected] Hyo Jung Shin [email protected] Yuhua Yin [email protected] Hyeok Hee Kwon [email protected] Hyewon Park [email protected]
Transl. Stroke Res.
Introduction Reactive oxygen species (ROS) are components of cellular metabolism in healthy cells and serve as a defense mechanism. The concentration of ROS is balanced, such that low conc
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