3-nitrotyrosine and Neurilemmoma

Schwann cells may be involved in the pathogenesis of several neuropathies, such as those linked to an excess of d-glucose. Indeed, hyperglicemic condition can often result in the production of high reactive/nitrosative oxygen species concentration and possible damage of several cell structures. In the present work attention has been focused on the possible nitrosative effect of hyperglycemia on RT4 Schwannoma cell lines.. Cells were cultured for 72hrs in the presence of 180 mM D-glucose. Morphology, growth rate, cell viability, catalase evaluation and Western blot were performed.. In D-glucose-exposed cells, 3-Nitrotyrosine increase and subsequent modifications in cell morphology, growth rate, viability and catalase activity were found.. Our findings suggested a possible primary role played by Schwann cells in the hyperglicemic neuropathy pathogenesis, through the excessive production of RNS and a decrease in antioxidant defense systems, bearing out the importance of the "nitrosative hypothesis" in the hyperglicemic-induced nervous system complications.

Topics: Animals; Catalase; Cell Line, Tumor; Cell Proliferation; Cell Survival; Diabetic Neuropathies; Glucose; Hyperglycemia; Neurilemmoma; Oxidative Stress; Rats; Reactive Nitrogen Species; Schwann Cells; Tyrosine

Schwannomas, particularly of vestibular origin, often accompany degenerative hypocellular areas known as Antoni B patterns; however, the detailed mechanism is uncertain. Eosinophilic hyaline droplets (EHD), the substantial nature of which are autophagic vacuoles, preferentially appear in acoustic schwannomas and distribute around areas of Antoni B. We investigated their common background using schwannomas with (15 cases) or without (10 cases) EHD, and demonstrated that EHD showed selective immunoreactivity with an anti-nitrotyrosine antibody, suggesting the overproduction of nitric oxide in this condition. The expression of inducible nitric oxide synthase was emphasized in infiltrating macrophages around hyalinized vessels. Protein-bound 4-hydroxy 2-nonenal, another oxidative stress marker, was detected in Antoni B tissue, but not in EHD. Antibodies to cleaved caspase-3 and single strand DNA, indicators of apoptosis, did not label tumors cells in Antoni B areas as well as EHD-bearing cells. The morphology and the mitotically static state of EHD-laden cells are phenotypically similar to autophagic cell death; however, autophagy in normal cells is a cell survival strategy against starvation, so the possibility remains that EHD are formed in that context. In either case, schwannomas may show a characteristic autophagic change by an endogenous mechanism. Tumor growth in a narrow intracranial space and resultant ischemia by self-oppression were postulated to be an initial event, because ischemia-reperfusion injury is a major source of reactive oxygen species and ischemia is also a potent trigger of autophagy as well as of tissue degeneration. Moreover, potential roles of chemokines and hemosiderosis are discussed.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Apolipoproteins D; Autophagy; Caspase 3; Deoxyguanosine; Female; Humans; Hyalin; Immunohistochemistry; Inclusion Bodies; Male; Middle Aged; Neurilemmoma; Nitric Oxide Synthase Type II; Oxidative Stress; Tyrosine