Iron promotes the survival and neurite extension of serum-starved PC12 cells in the presence of NGF by enhancing cell attachment.
Delayed death of serum-starved PC12 cells on a poly-L-lysine (PLL) matrix was observed, even in the presence of NGF. NGF blocked the apoptotic death of attached but not detached cells, which suggests that delayed death may be related to cell detachment from the PLL matrix. Iron selectively blocked this anoikis-like death by increasing cell attachment. Interestingly, the addition of > 10 microM FeCl2 to the culture medium generated gelatinous iron precipitates, and the removal of the precipitates abolished the iron effect. Attachment experiments using poly-HEMA supported the role of iron precipitates on cell-to-matrix adhesion. The expression of integrin beta1, neither N-cadherin nor alpha/beta-catenin, was also significantly increased by iron. In addition to its effect on cell viability, iron promoted the outgrowth of neurites. Our results collectively indicate that iron functions as a necessary co-element for NGF by enhancing cell attachment, survival, and neurite extension.
Hong
Jin-hee
JH
Department of Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul 120-750, Korea.
Noh
Kyung-min
KM
Yoo
Young-eun
YE
Choi
So-young
SY
Park
Sun-young
SY
Kim
Yoon-hee
YH
Chung
Jun-mo
JM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure; D016895:Culture Media, Serum-Free; D053938:DNA Fragmentation; D005296:Ferrous Compounds / Q000494:pharmacology*; D019012:Integrin beta1 / Q000502:physiology; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects*; D016716:PC12 Cells / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats
D002843:Chromatin; D016895:Culture Media, Serum-Free; D005296:Ferrous Compounds; D019012:Integrin beta1; D020932:Nerve Growth Factor; C029451:ferrous chloride