Chloride channel blocker 4,4-diisothiocyanatostilbene-2,2′-disulfonic acid inhibits nitric oxide-induced apoptosis in cultured rat hippocampal neurons

摘要

Apoptosis in cultured rat hippocampal neurons was induced using the nitric oxide donor 3-morpholinosydnonimine, and cells were treated with the chloride channel blocker, 4,4- diisothiocyanatostilbene-2,2'-disulfonic acid. Results showed that the survival rate of neurons was significantly increased after treatment with 4,4-diisothiocyanatostilbene-2,2'-disulfonic acid, and the rate of apoptosis decreased. In addition, the expression of the apoptosis-related proteins poly(adenosine diphosphate-ribose)polymerase-1 and apoptosis-inducing factor were significantly reduced. Our experimental findings indicate that the chloride channel blocker 4,4- diisothiocyanatostilbene-2,2'-disulfonic acid can antagonize apoptotic cell death of hippocampal neurons by inhibiting the expression of the apoptosis-related proteins poly(adenosine diphosphate-ribose)polymerase-1 and apoptosis-inducing factor. Research Highlights (1) 3-morpholinosydnonimine (1.0 mM) can significantly induce apoptosis in rat hippocampal neurons. (2) When poly(adenosine diphosphate-ribose)polymerase-1 and apoptosis-inducing factor were simultaneously expressed, neuronal apoptosis was evident. (3) Poly(adenosine diphosphate-ribose)polymerase-1 and apoptosis-inducing factor contribute to neural damage following ischemia. (4) 4,4-diisothiocyanatostilbene-2,2'-disulfonic acid (0.1 mM) can antagonize the expression of poly(adenosine diphosphate-ribose)polymerase-1 and apoptosis-inducing factor via a caspase independent signaling pathway. (5) The chloride channel blocker 4,4-diisothiocyanatostilbene-2,2'-disulfonic acid can protect neurons by inhibiting the caspase-dependent and -independent signaling pathways. Abbreviations PARP-1, poly(adenosine diphosphate-ribose)polymerase-1; AIF, apoptosis-inducing factor; DIDS, 4,4-diisothiocyanatostilbene-2,2'-disulfonic acid; NO, nitric oxide; SIN-1, 3-morpholinosydnonimine