PMID- 26559686 OWN - NLM STAT- MEDLINE DCOM- 20161110 LR - 20181113 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 41 IP - 4 DP - 2016 Apr TI - Heme Oxygenase-1 Protects Neurons from Ischemic Damage by Upregulating Expression of Cu,Zn-Superoxide Dismutase, Catalase, and Brain-Derived Neurotrophic Factor in the Rabbit Spinal Cord. PG - 869-79 LID - 10.1007/s11064-015-1764-1 [doi] AB - In the present study, we investigated the protective effects of heme oxygenase (HO-1) against ischemic damage in motor neurons of the rabbit spinal cord. A PEP-1-HO-1 fusion protein was made to and confirmed the effective the penetration of HO-1 into spinal cord neurons at 8 h after treatment. Transient spinal cord ischemia was induced by occlusion of the abdominal aorta for 15 min. Vehicle (glycerol) or 0.375 mg/kg PEP-1-HO-1 was administered intraperitoneally to rabbits immediately after ischemia/reperfusion. Animals were sacrificed 15 min after reperfusion to measure lactate levels; 24 h after reperfusion to measure caspase 3 and myeloperoxidase levels, lipid peroxidation, and the activity of Cu,Zn-superoxide dismutase (SOD1) and catalase (CAT); or 72 h after reperfusion to assess neuronal survival and measure the levels of brain-derived neurotrophic factor (BDNF) in spinal cord homogenates. Administration of PEP-1-HO-1 did not significantly alter arterial blood gases (PaCO2 and PaO2), pH, or blood glucose levels before ischemia, 10 min after occlusion, or 10 min after reperfusion. Mean arterial pressure was selectively reduced 10 min after occlusion. Administration of PEP-1-HO-1 improved the rabbit Tarlov scores, and increased neuronal survival, as assessed by NeuN immunohistochemical staining 72 h after ischemia/reperfusion. In addition, administration of PEP-1-HO-1 significantly ameliorated lactate accumulation 15 min after reperfusion, and the increases in caspase 3, myeloperoxidase, and lipid peroxidation 24 h after reperfusion. PEP-1-HO-1 administration significantly mitigated the decrease in SOD1 and CAT 24 h after reperfusion, and reversed the decrease in BDNF levels in spinal cord homogenates 72 h after ischemia/reperfusion. These results suggest that PEP-1-HO-1 can protect against neuronal damage after transient spinal cord ischemia by limiting early lactic acidosis and increasing SOD1, CAT, and BDNF levels. FAU - Jung, Hyo Young AU - Jung HY AD - Department of Anatomy and Cell Biology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea. FAU - Kim, Dae Won AU - Kim DW AD - Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangneung-Wonju National University, Gangneung, 210-702, South Korea. FAU - Yim, Hee Sun AU - Yim HS AD - Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangneung-Wonju National University, Gangneung, 210-702, South Korea. FAU - Yoo, Dae Young AU - Yoo DY AD - Department of Anatomy and Cell Biology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea. FAU - Kim, Jong Whi AU - Kim JW AD - Department of Anatomy and Cell Biology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea. FAU - Won, Moo-Ho AU - Won MH AD - Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea. FAU - Yoon, Yeo Sung AU - Yoon YS AD - Department of Anatomy and Cell Biology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea. FAU - Choi, Soo Young AU - Choi SY AD - Department of Biomedical Sciences, Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 200-702, South Korea. sychoi@hallym.ac.kr. FAU - Hwang, In Koo AU - Hwang IK AD - Department of Anatomy and Cell Biology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea. vetmed2@snu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151111 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 0 (Recombinant Fusion Proteins) RN - 33X04XA5AT (Lactic Acid) RN - EC 1.11.1.6 (Catalase) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.14.14.18 (PEP-1-heme oxygenase-1 fusion protein) RN - EC 1.15.1.1 (Superoxide Dismutase) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Catalase/*metabolism MH - Heme Oxygenase-1/*pharmacology MH - Ischemia/metabolism/pathology/physiopathology MH - Lactic Acid/metabolism MH - Male MH - Motor Neurons/*drug effects/metabolism/pathology MH - Neuroprotective Agents/*pharmacology MH - Rabbits MH - Recombinant Fusion Proteins/*pharmacology MH - Spinal Cord/blood supply/*drug effects/metabolism/pathology MH - Superoxide Dismutase/*metabolism MH - Up-Regulation OTO - NOTNLM OT - Anti-inflammation OT - Antioxidants OT - Brain-derived neurotrophic factor OT - Heme oxygenase-1 OT - Lactate OT - Neuroprotection OT - Transient spinal cord ischemia EDAT- 2015/11/13 06:00 MHDA- 2016/11/12 06:00 CRDT- 2015/11/13 06:00 PHST- 2015/07/23 00:00 [received] PHST- 2015/11/05 00:00 [accepted] PHST- 2015/10/19 00:00 [revised] PHST- 2015/11/13 06:00 [entrez] PHST- 2015/11/13 06:00 [pubmed] PHST- 2016/11/12 06:00 [medline] AID - 10.1007/s11064-015-1764-1 [pii] AID - 10.1007/s11064-015-1764-1 [doi] PST - ppublish SO - Neurochem Res. 2016 Apr;41(4):869-79. doi: 10.1007/s11064-015-1764-1. Epub 2015 Nov 11.