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Bilirubin oxidation end product B prevents CoCl2-induced primary cortical neuron apoptosis by promoting cell survival Akt/mTOR/p70S6K signaling pathway.
- Source :
-
Biochemical & Biophysical Research Communications . Apr2022, Vol. 602, p27-34. 8p. - Publication Year :
- 2022
-
Abstract
- Bilirubin oxidation end products (BOXes) are associated with the late-developing neurological deficits after subarachnoid hemorrhage (SAH) possibly by direct constricting the cerebral arteries, but their specific impacts on neurons especially in the state of hypoxia, a prominent feature during the late stage of SAH, remain unclear. Here, we explored the effects of BOXes on the primary cortical neurons subjected to CoCl 2 -induced hypoxia by evaluating the morphological and apoptotic changes of neurons. The present study showed that Z-BOX B but not Z-BOX A greatly alleviated CoCl 2 -induced neuronal cell deterioration and apoptosis. Immunocytochemical staining assay showed Z-BOX B significantly increased neurite length, the numbers of both secondary and tertiary branches, and the protein level of Synaptophysin. Caspase 3/7 apoptosis assay and DAPI staining showed that Z-BOX B markedly reduced primary cortical neurons apoptosis. The expression of cleaved Caspase-3 was suppressed by Z-BOX B treatment, while the expression of Bcl-xL was upregulated. To further discover the mechanism of the neuroprotective effect observed in Z-BOX B, we found Z-BOX B increased the expression of p-mTOR, p-Akt, and p-p70S6K. In general, our results implicated Z-BOX B may prevent CoCl 2 -induced primary cortical neurons apoptosis by activating sAkt/mTOR/p70S6K signaling pathway. Hence, the present data may provide new insights into the pathophysiological mechanism of delayed neurological dysfunction after SAH and novel targets for treating SAH. • Z-BOX B, but not Z-BOX A, exerted neuroprotective effect on CoCl2-challenged primary cortical neurons. • Z-BOX B alleviated neuronal apoptosis induced by CoCl2. • Z-BOX B reduced the expression of CoCl2-induced apoptotic proteins. • Z-BOX B promoted Akt/mTOR/p70S6K signaling pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 602
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 155861478
- Full Text :
- https://doi.org/10.1016/j.bbrc.2022.02.063