title: The potential role of JAK2/STAT3 pathway on the anti-apoptotic effect of recombinant human erythropoietin (rhEPO) after experimental traumatic brain injury of rats.
abstract: Previous studies indicate that administration of recombinant human erythropoietin (rhEPO) protects cortical neurons following traumatic brain injury (TBI). The mechanisms of rhEPO's neuroprotection are complex and interacting, including anti-apoptosis. Here we aim to demonstrate the role of janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway on the anti-apoptotic effect of rhEPO in Feeney free falling TBI model. Activation of JAK2/STAT3 in pericontusional cortex was analyzed among rats in Sham, TBI, TBI+rhEPO, TBI+rhEPO+AG490 groups (rhEPO: 5000 U/kg day; JAK2 inhibitor AG490: 5 mg/kg day, intraperitoneal) through Western blotting, electrophoretic mobility shift assay. Bcl-2 and Bcl-xl expression (Q-PCR, Western blotting) and cell apoptosis (TUNEL) in pericontusional cortex were also detected in each group. As a result, we found that TBI could activate JAK2 and STAT3, and increase cell apoptosis in pericontusional cortex. RhEPO enhanced the expression of p-JAK2 and p-STAT3, up-regulated the mRNA and protein levels of Bcl-2 and Bcl-xl, followed by increased cell survival. Moreover, AG490 attenuated rhEPO's neuroprotection by down-regulating rhEPO-induced activation of JAK2/STAT3, and inhibiting Bcl-2 and Bcl-xl. These results suggest the essential role of JAK2/STAT3 pathway on the anti-apoptotic benefit of post-TBI rhEPO treatment.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Jiangsu Province, Nanjing 210002, PR China.
authors.forename: Jinbing
authors.initials: J
authors.lastname: Zhao
authors.forename: Guangzhao
authors.initials: G
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xingfen
authors.initials: X
authors.lastname: Su
authors.forename: Chunhua
authors.initials: C
authors.lastname: Hang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D015153:Blotting, Western; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D020032:Tyrphostins / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D017931:DNA Primers; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D004921:Erythropoietin