title: Neuro-protective effects of growth hormone (GH) after hypoxia-ischemia injury in embryonic chicken cerebellum.
abstract: Neuroprotection is a mechanism within the central nervous system (CNS) that protects neurons from damage as a result of a severe insult. It is known that growth hormone (GH) is involved in cell survival and may inhibit apoptosis in several cell types, including those of the CNS. Both GH and GH-receptor (GHR) genes are expressed in the cerebellum. Thus, we investigated the possible neuroprotective role of GH in this organ, which is very sensitive to hypoxic/ischemic conditions. Endogenous GH levels increased in the brain and cerebellum (30% and 74%, respectively) of 15-day-old chicken embryos exposed to hypoxia during 24h compared to normoxia. In primary embryonic cerebellar neuron cultures treated under hypoxia (0.5% O(2)) and low glucose (1g/L) conditions (HLG) for 1h, GH levels increased 1.16-fold compared to the control. The addition of 1nM recombinant chicken GH (rcGH) to cultures during HLG increased cell viability (1.7-fold) and the expression of Bcl-2 (1.67-fold); in contrast the caspase-3 activity and the proportion of apoptotic cells decreased (37% and 54.2%, respectively) compared to HLG. rcGH activated the PI3K/Akt pathway both under normoxic and HLG conditions, increasing the proportion of phosphorylated Akt (1.7- and 1.4-fold, respectively). These effects were abolished by wortmannin and by immunoneutralization, indicating that GH acts through this signaling pathway. Furthermore, the 15-kDa GH variant (10nM) significantly increased cell viability and decreased caspase-3 activity during HLG condition. Thus GH may act as a paracrine/autocrine neuroprotective factor that preserves cellular viability and inhibits apoptotic cell death.
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, Mexico.
authors.forename: Clara
authors.initials: C
authors.lastname: Alba-Betancourt
authors.forename: José Luis
authors.initials: JL
authors.lastname: Luna-Acosta
authors.forename: Candy Elizabeth
authors.initials: CE
authors.lastname: Ramírez-Martínez
authors.forename: Daniela
authors.initials: D
authors.lastname: Avila-González
authors.forename: Estefany
authors.initials: E
authors.lastname: Granados-Ávalos
authors.forename: Martha
authors.initials: M
authors.lastname: Carranza
authors.forename: Hilda
authors.initials: H
authors.lastname: Martínez-Coria
authors.forename: Carlos
authors.initials: C
authors.lastname: Arámburo
authors.forename: Maricela
authors.initials: M
authors.lastname: Luna
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D018696:Neuroprotective Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013006:Growth Hormone; D000077191:Wortmannin