Cell attachment and neurite stability in NG108-15 cells: effects of 5'-deoxy, 5'-methyl thioadenosine (MTA) compared with laminin, kinase inhibitor H-7, and Mn2+ ions.
Methylation inhibitors such as 5'-deoxy, 5'-methyl thioadenosine (MTA) have been shown to exert an intriguing spectrum of effects upon neural cells: inhibiting responses to nerve growth factor in PC12 cells; stimulating outgrowth of rapid-onset neurites in NG108-15 cells; inhibiting the resorption and remodelling of these rapid-onset neurites; and inducing fibroblasts to extend long, multipolar, branched processes. To learn whether the apparently diverse effects of these agents might reflect some common underlying cellular sites of action, we examined simpler, short-term effects of MTA upon cell attachment and stability of rapid-onset neurites in NG108-15 cells, and compared the effects with those produced by the kinase inhibitor H-7, substratum-bound laminin, or Mn2+ ions. MTA was shown to selectively enhance the response of cells and their neurites in attaching to their substrata, without inducing other 'adhesive' responses such as cell spreading or motility. The data suggest that MTA activates or increases the effectiveness of 'attachment receptors', and that this at least partially explains its neurite-promoting effects. While it is still premature to propose a common mechanism of action for MTA and related agents, all of their known effects thus appear to involve modulating responses generated at cell-surface receptors. A further clue is that kinase C activity appears to be critical, since cells pretreated with phorbol esters for 24 h (which down-regulated levels of kinase C) selectively failed to extend neurites in response to MTA, but responded normally to laminin and Mn2+ ions.
Smalheiser
N R
NR
Department of Pediatrics, Kennedy Center, University of Chicago, IL 60637.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D003839:Deoxyadenosines; D007546:Isoquinolines / Q000494:pharmacology*; D007797:Laminin / Q000494:pharmacology*; D008345:Manganese / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D013872:Thionucleosides / Q000494:pharmacology*
D003839:Deoxyadenosines; D007546:Isoquinolines; D007797:Laminin; D009414:Nerve Growth Factors; D010879:Piperazines; D013872:Thionucleosides; D008345:Manganese; C008500:5'-methylthioadenosine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000241:Adenosine