title: Mitochondrial Dihydrolipoamide Dehydrogenase is Upregulated in Response to Intermittent Hypoxic Preconditioning.
abstract: Intermittent hypoxia preconditioning (IHP) has been shown to protect neurons against ischemic stroke injury. Studying how proteins respond to IHP may identify targets that can help fight stroke. The objective of the present study was to investigate whether mitochondrial dihydrolipoamide dehydrogenase (DLDH) would respond to IHP and if so, whether such a response could be linked to neuroprotection in ischemic stroke injury. To do this, we subjected male rats to IHP for 20 days and measured the content and activity of DLDH as well as the three α-keto acid dehydrogenase complexes that contain DLDH. We also measured mitochondrial electron transport chain enzyme activities. Results show that DLDH content was indeed upregulated by IHP and this upregulation did not alter the activities of the three α-keto acid dehydrogenase complexes. Results also show that the activities of the five mitochondrial complexes (I-V) were not altered either by IHP. To investigate whether IHP-induced DLDH upregulation is linked to neuroprotection against ischemic stroke injury, we subjected both DLDH deficient mouse and DLDH transgenic mouse to stroke surgery followed by measurement of brain infarction volume. Results indicate that while mouse deficient in DLDH had exacerbated brain injury after stroke, mouse overexpressing human DLDH also showed increased brain injury after stroke. Therefore, the physiological significance of IHP-induced DLDH upregulation remains to be further investigated.
authors.affiliation: 1. Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA ; 2. Department of Anethesiology, the First Affiliated Hospital of Nanjing University, Nanjing, Jiangsu province, China, 210029.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Li
authors.affiliation: 1. Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA ; 3. Department of Biochemistry and Molecular Biology, Gannan Medical University, Ganzhou, Jiangxi province, China, 341000.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Luo
authors.affiliation: 1. Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Jinzi
authors.initials: J
authors.lastname: Wu
authors.affiliation: 4. Department of Pharmacology and Neurosciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Nopporn
authors.initials: N
authors.lastname: Thangthaeng
authors.affiliation: 4. Department of Pharmacology and Neurosciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Marianna E
authors.initials: ME
authors.lastname: Jung
authors.affiliation: 1. Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA ; 5. College of Life Sciences and Technology, Xinjiang University, Urumqi, Xinjiang, China, 830046.
authors.forename: Siqun
authors.initials: S
authors.lastname: Jing
authors.affiliation: 1. Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Linya
authors.initials: L
authors.lastname: Li
authors.affiliation: 1. Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Dorette Z
authors.initials: DZ
authors.lastname: Ellis
authors.affiliation: 6. Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China 210029.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: 2. Department of Anethesiology, the First Affiliated Hospital of Nanjing University, Nanjing, Jiangsu province, China, 210029.
authors.forename: Zhengnian
authors.initials: Z
authors.lastname: Ding
authors.affiliation: 4. Department of Pharmacology and Neurosciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Forster
authors.affiliation: 1. Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Liang-Jun
authors.initials: LJ
authors.lastname: Yan
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D008058:Dihydrolipoamide Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D006801:Humans; D019194:Ischemic Preconditioning; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation
chemical_list: D045222:Electron Transport Chain Complex Proteins; D008058:Dihydrolipoamide Dehydrogenase
keywords: dihydrolipoamide dehydrogenase; intermittent hypoxic preconditioning; ischemic stroke; mitochondria; neuroprotection