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Role of caspase-1 activation in bilirubin-induced injury in cultured primary rat hippocampal neurons / 南方医科大学学报
Journal of Southern Medical University ; (12): 567-571, 2018.
Article in Chinese | WPRIM | ID: wpr-690429
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of caspase-1 activation in bilirubin-induced neuronal injury and the protective effect of VX-765 against bilirubin-induced neurotoxicity in cultured primary rat hippocampal neurons.</p><p><b>METHODS</b>Cultured primary rat hippocampal neurons were exposed to DMSO (control group), 50 µmol/L bilirubin, or 50 µmol/L bilirubin 1 h after 50 µmol/L VX-765 treatment. The expressions of NLRP3 and caspase-1 in the neurons were detected by Western blotting, and the relative cell survival and death rates were assessed with a modified MTT assay, lactate dehydrogenase assay and Typan blue staining. Interleukin-18 (IL-18) concentration in the culture supernatant was measured using enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>In cultured primary rat hippocampal neurons, bilirubin exposure for 3 and 6 h caused significant increases in the expressions of NLRP3 and activated caspase-1 compared with those in the control group (P<0.05). Pretreatment of the cells with VX-765 obviously suppressed bilirubin-induced activation of caspase-1 (P<0.05). The relative survival rate of the neurons was (84.02∓2.31)% in VX-765 intervention group, significantly higher than that in bilirubin group (P<0.05) but lower than that in the control group (P<0.05); LDH release rate in VX-765 intervention group was (10.78∓1.58)%, significantly lower than that in bilirubin group (P<0.05) but higher than that in the control group (P<0.05). The cell death rate in VX-765 intervention group was (5.58∓1.23)%, significantly lower than that in bilirubin group (P<0.05) but higher than that in the control group (P<0.05).</p><p><b>CONCLUSION</b>In cultured primary rat hippocampal neurons, caspase-1 activation plays a role in bilirubin-induced neurotoxicity, and VX-765 treatment provides protection against bilirubin-induced neuronal injury by inhibiting caspase-1 activation.</p>
Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Journal of Southern Medical University Year: 2018 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Journal of Southern Medical University Year: 2018 Type: Article