Protein tyrosine nitration is associated with cold- and drug-resistant microtubules in neuronal-like PC12 cells.
Among the myriad of cellular functions played by nitric oxide in the brain, there is increasing evidence that nitric oxide might be a primary player in the program of neurogenesis and neuronal differentiation. We have recently reported that tyrosine nitration of proteins is implicated in the signaling pathway triggered by nitric oxide during NGF-induced neuronal differentiation in PC12 cells. The cytoskeleton becomes the main cellular fraction containing nitrotyrosinated proteins, and the cytoskeletal proteins alpha-tubulin and tau are two of the targets. Here, we have studied the association of nitrated proteins with the cytoskeletal fraction in differentiating PC12 cells following exposure to microtubule depolymerising treatments and found that nitration of the cytoskeleton correlates with the increased microtubule stability underlying the progression of neuronal differentiation. These results suggest a novel functional role for nitrated cytoskeletal proteins in the stabilisation of neurites occurring in differentiated neuronal cells.
Department of Biology, University of Milano, Via Celoria 26, 20133 Milano, Italy. graziella.cappelletti@unimi.it
Graziella
G
Cappelletti
Maria Grazia
MG
Maggioni
Cristina
C
Ronchi
Rosalba
R
Maci
Gabriella
G
Tedeschi
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003080:Cold Temperature / Q000009:adverse effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004351:Drug Resistance / Q000502:physiology; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D014443:Tyrosine / Q000378:metabolism*
D000970:Antineoplastic Agents; D009419:Nerve Tissue Proteins; D009566:Nitrates; D009569:Nitric Oxide; D014443:Tyrosine; D020932:Nerve Growth Factor; D015739:Nocodazole