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TAT-mediated delivery of neuroglobin attenuates apoptosis induced by oxygen-glucose deprivation via the Jak2/Stat3 pathway in vitro.
Neurol Res. 2015 Jun; 37(6):531-8.NR

Abstract

OBJECTIVES

Neuroglobin (Ngb), an identified globin in vertebrate brain, is a potential novel protective protein against brain ischemia. In our previous study, the human immunodeficiency virus trans-activator of transcription (TAT) protein transduction domain successfully delivered exogenous Ngb into neurons in the mouse, and protected the brain from cerebral ischemia-induced apoptosis. The aim of this study is to investigate the role of TAT-Ngb in attenuating oxygen-glucose deprivation (OGD) induced apoptosis and to explore the possible mechanism.

METHODS

Nerve growth factor (NGF)-induced PC12 cells were divided into (1) the control group, (2) the OGD group (just OGD), (3) the Ngb treatment group (OGD and Ngb treatment), and (4) the TAT-Ngb treatment group (OGD and TAT-Ngb treatment). Cell viability and apoptosis were assessed by the MTT assay and the AnnexinV/propidium iodide (PI) staining, respectively. The mitochondrial transmembrane potential was measured by JC-1 staining. Caspase-3, Bcl-2, Bax, Stat3, Jak2, and Akt were determined by western blot analysis.

RESULTS

Trans-activator of transcription effectively delivered Ngb into NGF-induced PC12 cells. Neuroglobin-mediated neuroprotection rescued cultured cells from OGD. We also confirmed previous findings that TAT-Ngb inhibited mitochondrial apoptosis following OGD. Inhibition of apoptosis by Ac-DEVD-CHO showed that caspase-3 was a crucial factor in OGD-induced apoptosis cascades. AG490, a specific Jak2 inhibitor, attenuated the protective effects of TAT-Ngb. The TAT-Ngb promoted expression of the anti-apoptotic protein Bcl-2 through the Jak2/Stat3 signal pathway, and inhibited apoptosis by blocking caspase-3 activation, while the Jak-Akt-Stat3 signal network was not involved.

CONCLUSION

Our results demonstrate that TAT-Ngb can protect neuron-like cells against OGD-induced apoptosis by activating the Jak2/Stat3 pathway.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25023896

Citation

Lin, Yi, et al. "TAT-mediated Delivery of Neuroglobin Attenuates Apoptosis Induced By Oxygen-glucose Deprivation Via the Jak2/Stat3 Pathway in Vitro." Neurological Research, vol. 37, no. 6, 2015, pp. 531-8.
Lin Y, Cai B, Xue XH, et al. TAT-mediated delivery of neuroglobin attenuates apoptosis induced by oxygen-glucose deprivation via the Jak2/Stat3 pathway in vitro. Neurol Res. 2015;37(6):531-8.
Lin, Y., Cai, B., Xue, X. H., Fang, L., Wu, Z. Y., & Wang, N. (2015). TAT-mediated delivery of neuroglobin attenuates apoptosis induced by oxygen-glucose deprivation via the Jak2/Stat3 pathway in vitro. Neurological Research, 37(6), 531-8. https://doi.org/10.1179/1743132814Y.0000000420
Lin Y, et al. TAT-mediated Delivery of Neuroglobin Attenuates Apoptosis Induced By Oxygen-glucose Deprivation Via the Jak2/Stat3 Pathway in Vitro. Neurol Res. 2015;37(6):531-8. PubMed PMID: 25023896.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TAT-mediated delivery of neuroglobin attenuates apoptosis induced by oxygen-glucose deprivation via the Jak2/Stat3 pathway in vitro. AU - Lin,Yi, AU - Cai,Bin, AU - Xue,Xie-Hua, AU - Fang,Ling, AU - Wu,Zhi-Ying, AU - Wang,Ning, Y1 - 2014/07/15/ PY - 2014/7/16/entrez PY - 2014/7/16/pubmed PY - 2016/3/2/medline KW - Apoptosis, KW - Jak2/Stat3 KW - Neuroglobin, KW - Oxygen–glucose deprivation, KW - Protein transduction domain, SP - 531 EP - 8 JF - Neurological research JO - Neurol Res VL - 37 IS - 6 N2 - OBJECTIVES: Neuroglobin (Ngb), an identified globin in vertebrate brain, is a potential novel protective protein against brain ischemia. In our previous study, the human immunodeficiency virus trans-activator of transcription (TAT) protein transduction domain successfully delivered exogenous Ngb into neurons in the mouse, and protected the brain from cerebral ischemia-induced apoptosis. The aim of this study is to investigate the role of TAT-Ngb in attenuating oxygen-glucose deprivation (OGD) induced apoptosis and to explore the possible mechanism. METHODS: Nerve growth factor (NGF)-induced PC12 cells were divided into (1) the control group, (2) the OGD group (just OGD), (3) the Ngb treatment group (OGD and Ngb treatment), and (4) the TAT-Ngb treatment group (OGD and TAT-Ngb treatment). Cell viability and apoptosis were assessed by the MTT assay and the AnnexinV/propidium iodide (PI) staining, respectively. The mitochondrial transmembrane potential was measured by JC-1 staining. Caspase-3, Bcl-2, Bax, Stat3, Jak2, and Akt were determined by western blot analysis. RESULTS: Trans-activator of transcription effectively delivered Ngb into NGF-induced PC12 cells. Neuroglobin-mediated neuroprotection rescued cultured cells from OGD. We also confirmed previous findings that TAT-Ngb inhibited mitochondrial apoptosis following OGD. Inhibition of apoptosis by Ac-DEVD-CHO showed that caspase-3 was a crucial factor in OGD-induced apoptosis cascades. AG490, a specific Jak2 inhibitor, attenuated the protective effects of TAT-Ngb. The TAT-Ngb promoted expression of the anti-apoptotic protein Bcl-2 through the Jak2/Stat3 signal pathway, and inhibited apoptosis by blocking caspase-3 activation, while the Jak-Akt-Stat3 signal network was not involved. CONCLUSION: Our results demonstrate that TAT-Ngb can protect neuron-like cells against OGD-induced apoptosis by activating the Jak2/Stat3 pathway. SN - 1743-1328 UR - https://www.unboundmedicine.com/medline/citation/25023896/TAT_mediated_delivery_of_neuroglobin_attenuates_apoptosis_induced_by_oxygen_glucose_deprivation_via_the_Jak2/Stat3_pathway_in_vitro_ L2 - https://www.tandfonline.com/doi/full/10.1179/1743132814Y.0000000420 DB - PRIME DP - Unbound Medicine ER -