Date of Award
12-17-2002
Document Type
Thesis
Abstract
A dynamic actin cytoskeleton in central nervous system (CNS) neurons is pivotal for regeneration. Following acute CNS trauma, the proinflammatory cytokines TNF[alpha] and IL-1[beta] become expressed in cells and induce Rac 1-mediated actin filament reorganization. Also, Rac 1 regulates a NAD(P)H oxidase activity that generates superoxide (·O₂). This study's objective was to determine whether TNF[alpha] and/or IL-1[beta] induce a Rac 1-dependent actin filament reorganization in SH-SY5Y neuroblastoma cells and in chick spinal cord neurons via the signaling intermediate, superoxide. SH-SY5Y cells respond to soluble TNF[alpha] or IL-1[beta] with transient, biphasic actin filament reorganization. Over a time period of 30 min, increased membrane ruffling precedes formation of stress fibers and arrest of cell motility, compared to controls. Similarly, in chick growth cones soluble TNF[alpha] or IL-1[beta] for 15 and 30 minute time periods caused increased lamellipodia formation. The actin filament reorganization in both SH-SY5Y cells and chick spinal cord neurons was inhibited by DPI, an irreversible inhibitor of NAD(P)H oxidase, and MnTBAP, a superoxide dismutase mimetic. Conclusively, TNF[alpha] and IL-1[beta] a transient Rac 1-mediated actin filament reorganization, which could block regeneration of injured axons. Our findings that DPI and MnTBAP prevent this reorganization reveals a potential therapy to mitigate the inflammatory response.
Recommended Citation
Smeets, Shelli Stewart, "Proinflammatory cytokines induce a Rac1-mediated superoxide-dependent reorganization of the actin cytoskeleton in neuronal cells" (2002). Chemistry and Biochemistry. 21.
https://ualaska.researchcommons.org/uaf_grad_chem_biochem/21
Handle
http://hdl.handle.net/11122/5001