Journal article
Tissue inhibitor of matrix metalloproteinase-1 mediates erythropoietin-induced neuroprotection in hypoxia ischemia
Neurobiology of disease, Vol.44(1), pp.28-37
2011
DOI: 10.1016/j.nbd.2011.05.020
PMCID: PMC3153566
PMID: 21689752
Abstract
Previous studies have shown that erythropoietin (EPO) is neuroprotective in both in vivo and in vitro models of hypoxia ischemia. However these studies hold limited clinical translations because the underlying mechanism remains unclear and the key molecules involved in EPO-induced neuroprotection are still to be determined. This study investigated if tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and its upstream regulator signaling molecule Janus kinase-2 (JAK-2) are critical in EPO-induced neuroprotection. Hypoxia ischemia (HI) was modeled in-vitro by oxygen and glucose deprivation (OGD) and in-vivo by a modified version of Rice–Vannucci model of HI in 10-day-old rat pups.
EPO treated cells were exposed to AG490, an inhibitor of JAK-2 or TIMP-1 neutralizing antibody for 2
h with OGD. Cell death, phosphorylation of JAK-2 and signal transducers and activators of transcription protein-3 (STAT-3), TIMP-1 expression, and matrix metalloproteinase-9 (MMP-9) activity were measured and compared with normoxic group. Hypoxic ischemic animals were treated one hour following HI and evaluated 48
h after. Our data showed that EPO significantly increased cell survival, associated with increased TIMP-1 activity, phosphorylation of JAK-2and STAT-3, and decreased MMP-9 activity in vivo and in vitro. EPO's protective effects were reversed by inhibition of JAK-2 or TIMP-1 in both models. We concluded that JAK-2, STAT-3 and TIMP-1 are key mediators of EPO-induced neuroprotection during hypoxia ischemia injury.
► TIMP-1 mediates EPO-induced neuroprotection. ► STAT-3 is necessary for EPO-induced neuroprotection. ► The above mediator of EPO was studied in vitro and in vivo.
Details
- Title: Subtitle
- Tissue inhibitor of matrix metalloproteinase-1 mediates erythropoietin-induced neuroprotection in hypoxia ischemia
- Creators
- Rhonda Souvenir - Loma Linda UniversityNancy Fathali - Loma Linda UniversityRobert P. Ostrowski - Loma Linda UniversityTim Lekic - Loma Linda UniversityJohn H. Zhang - Loma Linda UniversityJiping Tang - Loma Linda University
- Resource Type
- Journal article
- Publication Details
- Neurobiology of disease, Vol.44(1), pp.28-37
- DOI
- 10.1016/j.nbd.2011.05.020
- PMID
- 21689752
- PMCID
- PMC3153566
- NLM abbreviation
- Neurobiol Dis
- ISSN
- 0969-9961
- eISSN
- 1095-953X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2011
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359567702771
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