Participation of nitric oxide synthase (NOS) and atypical protein kinase C (PKC) in thyroid hormone-mediated apoptosis of murine T lymphocytes.

GRACIELA ALICIA CREMASCHI; ALICIA J KLECHA; CLAUDIA VERCELLI; ANA MARÍA FRANCHI; ANA MARÍA GENARO; MARÍA LAURA BARREIRO ARCOS

Miami Beach

Congreso; 94th Annual Meeting of The American Association of Immunologists; 2007

The American Association of Inmunologist

TH regulate immune responses and are able to influence proliferation and differentiation in several cell types, but their direct actions on lymphocytes have not been elucidated. We have demonstrated that short time culture (up to 72 h) of quiescent BW5147 (BW) T cells in the presence of TH induced cell division. Here prolonged actions of TH on BW cells and the intracellular signals involved were studied. After 5 days of culture HT inhibited BW growth inducing apoptosis, as shown by Hoescht staining and DNA ladder assay. These effects were accompanied by an increase in NOS activity measured by [14C]-citrulline formation. Also, an increase in iNOS and a decrease in the PKC z isoform, both at the protein (by western blot analysis) and mRNA levels (by RT-PCR evaluation) were seen An increase in reactive oxygen species (determined by conversion of dichlorofluorescin-diacetate to the fluorescent DCF) was found. Additionally, TH induced an increment in protein nitrosylation.  These results show that prolonged HT exposition lead to an exacerbate increase in iNOS activity, that would in turn result in PKC z decrease, probably through protein nitrosylation. These intracellular signals would trigger apoptotic mechanisms involved in TH regulation of lymphocyte activity.