Comparison of S-nitrosoglutathione- and staurosporine-induced apoptosis in human neural cells.
S-nitrosoglutathione (GSNO) is an endogenously produced S-nitrosylating compound that controls the function of various proteins. While a number of rodent cell lines have been used to study GSNO-induced apoptosis, the mechanisms of action remain to be evaluated in human cells and in parallel with other common apoptosis-inducing agents. In this study, we compared the pro-apoptotic effects of GSNO and staurosporine (STS) on human neural progenitors (NT2, hNP1) and neuroblasts (SH-SY5Y). We show that these cells exhibit comparable levels of susceptibility to GSNO- and STS-induced apoptotic cell death, as demonstrated by condensed nuclei and CASP3 activation. Mechanistic differences in apoptotic responses were observed as differential patterns of DNA fragmentation and levels of BAX, BCL-XL, CASP8, and p-ERK in response to GSNO and STS treatment. Mitochondrial membrane potential analysis revealed that NT2 and hNP1 cells, but not SH-SY5Y cells, undergo mitochondrial hyperpolarization in response to short-term exposure to STS prior to undergoing subsequent depolarization. This is the first study to report differences in apoptotic responses to GSNO and STS in 3 complementary human neural cell lines. Furthermore, these cells represent useful tools in cell pharmacological paradigms in which susceptibility to apoptosis-inducing agents needs to be assessed at different stages of neural cell fate commitment and differentiation.
a Human Health Therapeutics, National Research Council Canada, 1200 Montreal Road, Ottawa, ON K1A 0R6, Canada.
Caroline
C
Sodja
Maria
M
Ribecco-Lutkiewicz
Julie
J
Haukenfrers
Fahar
F
Merchant
Willard J
WJ
Costain
Mahmud
M
Bani-Yaghoub
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000473:pathology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D026422:S-Nitrosoglutathione / Q000378:metabolism / Q000494:pharmacology*; D019311:Staurosporine / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; D018696:Neuroprotective Agents; D026422:S-Nitrosoglutathione; D019311:Staurosporine
BAX; BCL-XL; Bax; NT2; SH-SY5Y; caspase 3; caspase 8; caspase-3; caspase-8; cellules souches neurales; hNP1; mitochondria; mitochondrie; neural progenitors