Involvement of Bax and caspase-9 in heroin-induced apoptosis in cerebellar granule neurons via C-Jun pathway activation

Background: The cerebellum neuronal apoptosis cell is characteristic lesions of heroin spongiform leukoencephalopathy (HSLE), and the underlying mechanism of cerebellums usceptibility remains to be clarified. C-Jun signal pathway plays a vital role in apoptosis process. C-jun, Bax and Caspase-9, new identified proteins are highly associated with metastasis of many kinds of cell apoptosis, which were never reported in HSLE. Methods: The expression of C-jun, Bax and caspase-9 was detected by Hoechst 33342 staining, flow Cytometry, RT-PCR, Western blotting in normal group and inhibitor groups with Lentiviral, JNK inhibitor SP600125 or CEP1347 to further observe the morphological of cerebellum changes by electron microscopic scanning and studying on the protein expressions of C-jun, Bax and caspase-9 by immunohistochemistry and Western blotting in the rat model of heroin addiction. Results: The study found C-Jun pathway participated in the process of activating neuronal apoptosis by heroininduced apoptosis. Inhibitions of C-Jun/JNK pathway by Lentiviral, JNK inhibitor SP600125 or CEP1347 upstream blocker could lead to decrease Bax and caspase-9 factors expression. And cerebellum cytoplasm and nucleus appeared obvious morphological changes. C-jun, Bax and caspase-9 factors also showed high expression trend under the effect of heroin in rat. Conclusion: To explore the role of C-Jun pathway in the heroin-induced neuronal apoptosis, C-Jun protein involving in intrinsic apoptotic signaling pathway suggested that C-Jun signal pathway was activated by heroin, Bax and caspase-9 which were candidates target genes of C-Jun signal pathway in the apoptosis process.

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