SH-SY5Y細胞における一酸化窒素ドナーにより誘導される細胞死 Effects of nitric oxide (NO)-donors on cell death of SH-SY5Y, a human neuroblastoma cell line
Recently, it is known that NO is a cellular mediator with multiple biological functions including neurotoxicity and Bcl-2 inhibit a variety of a apoptotic deaths. We studied i) effects of several NO-related reagents on ADP-ribosylation, ii) effects of several kinase modulators on Bcl-2 expression, and iii) effects of several NO-donors on cell death of SH-SY5Y. NO-donors (SNP and SNAP) enhanced ADP-ribosylation of purified glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 37 kDa and 110 kDa proteins in SH-SY5Y, and 110 kDa proteins in rat fetal brain. SNP-enhanced ADP-ribosylation of GAPDH was inhibited by ADP-ribose. While, ADP-ribosylation of 110 kDa proteins in fetal brain was inhibited by benzamide. These results suggested that 37 kDa protein is GAPDH and 110 kDa protein is poly(ADP-ribose) synthetase. Although Bcl-2 is expressed in nontreated SH-SY5Y, Bcl-2 was more increased by PMA (a PKC activator), and was decreased by staurosporine (a PKC inhibitor) and dibutyryl cAMP (a PKA activator), suggesting that the expression of Bcl-2 is modulated by PKC and PKA. In addition, NO-donors induced cell death of SH-SY5Y in a concentrationdependent manner. From these results, we will discuss relationship between NO-donor, ADPribosylation and Bcl-2 in SH-SY5Y.
日本薬理学雑誌 106, 222-226, 1995-09-01