Neuronal differentiation of Neuro 2a cells by lactacystin and its partial inhibition by the protein phosphatase inhibitors calyculin A and okadaic acid.
Lactacystin (1.3 microM), a metabolite from an actinomycete, induced the formation of bipolar projections at both sides of the cell body of Neuro 2a cells 1 day after treatment and networks at and after 3 days and enhanced acetylcholinesterase activity (a marker of neuronal differentiation). Thus, the neuronal differentiation was characterized both morphologically and functionally. The experiments with various inhibitors of protein kinases and phosphatases revealed that the protein phosphatase inhibitors calyculin A (0.5 nM) and okadaic acid (0.6 nM) inhibit the formation of bipolar projections at 1 day, but does not inhibit the network formation at and after 3 days.
D000110:Acetylcholinesterase / Q000378:metabolism; D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D015415:Biomarkers / Q000032:analysis; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006873:Hydroquinones / Q000494:pharmacology; D007700:Kinetics; D008387:Marine Toxins; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D019319:Okadaic Acid; D010080:Oxazoles / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors; D011714:Pyrans; D013141:Spiro Compounds; D013997:Time Factors
D000935:Antifungal Agents; D015415:Biomarkers; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D006873:Hydroquinones; D008387:Marine Toxins; D010080:Oxazoles; D047428:Protein Kinase Inhibitors; D011714:Pyrans; D013141:Spiro Compounds; C053079:tautomycin; C067713:lactacystin; C084037:dephostatin; D019319:Okadaic Acid; D003994:Bucladesine; C059041:calyculin A; D000110:Acetylcholinesterase; D010749:Phosphoprotein Phosphatases; D000111:Acetylcysteine