Nitrosative-induced posttranslational α-tubulin changes on high-glucose-exposed Schwannoma cell line.
OBJECTIVE: One of the major complications during prolonged hyperglycemic condition is the onset of the so-called diabetic neuropathy, that can affect the peripheral nervous system. Evidence has reported that glucose-induced oxidative stress could be a key mediator in this process, impairing the cytoskeletal structures, such as microtubules. In general, much attention is paid to the possible nitrosative-induced changes of neurons during hyperglycemic conditions, while little is known of the Schwann cells.
METHODS: Using morphological examination, immunofluorescence staining and western blot analysis, the possible hyperglycemic oxidative-induced microtubular changes in the RT4 Schwannoma cell line was investigated.
RESULTS: After 72 hrs of 180 mM d-glucose exposure, a decrease of total, tyrosinated and detyrosinated α-tubulins was found, whereas a significant increase of the acetylated α-tubulin isotype and 3-nitro-l-tyrosine was present, both through western blot and immunofluorescence staining. Moreover a downregulation of catalase and deacetylase Sirt2 enzymes was detected.
CONCLUSION: Our data underline the importance of nitrosative-induced microtubular alterations in the PNS, during hyperglycemic conditions, highlighting that Schwann cells may be directly involved in the pathogenesis of diabetic neuropathy, through the impairment of their microtubular network....