Cerebral expression and serum detectability of secretagogin, a recently cloned EF-hand Ca2+-binding protein

Recently we identified a novel EF-hand Ca-binding protein termed secretagog in, which is expressed in neuroendocrine cells. Immunohistochemical investi gations, using a murine monoclonal and an affinity purified rabbit polyclon al anti-secretagogin antibody as well as Northern-blat and Western-blot ana lysis revealed a neuron-specific cerebral expression pattern. Secretagogin was detected in high quantity in basket and stellate cells of the cerebella r cortex, in secretary neurons of the anterior part of the pituitary gland and in singular neurons of the frontal and parietal neocortex. Remarkable s taining intensity was observed in hypothalamic and in hippocampal neurons. Using a newly developed sandwich capture ELISA we show presence of secretag ogin in serum of patients suffering from hypoxic neuronal damage. In sera o btained from 32 patients with different forms of neurological symptoms due to focal cerebral ischemia, secretagogin levels ranged from 3 to 236 pg/ml, with highest levels observed on days 2 and 3 after infarction. Three patie nts exhibiting minor, reversible neurological deficits had nondetectable se rum secretagogin levels at time points of testing. In 50 control sera, secr etagogin was below the detection limit of our ELISA. Parallel analysis of s ecretagogin and the established neurobiochemical marker S-100B in 14 repres entative patients revealed comparable results. However, S-100B levels were higher and exhibited different kinetics than secretagogin. Our data present the cerebral expression pattern of secretagogin and give evidence that thi s protein might represent a clinically relevant serum marker indicative for neuronal damage.