Up-regulation of NEP-activity of SK-N-SH cells by green tea extract and its natural products on risk of alzheimer

Abstract

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. AD is characterized pathologically by the accumulation of amyloid a-peptide as senile plaques in the brain. Neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) belong to the major At3-degrading enzymes. NEP and ACE are zinc-endopeptidases enzymes acting as ectoenzymes on the outer surface of different cells. In order to test the influence of green tea extract and some of its natural components (caffeine, theophylline, theanine, epicatechin and epigallocatechin), we used the neuroblastoma cell line SK-NSH, then we studied the changes in the specific cellular NEP and ACE activity after longterm treatment with these substances. Despite the high similarity between both enzymes ACE and NEP, green tea extract and the tested substances only influenced selectively the specific NEP activity without affecting the specific ACE activity. We have also shown that dibutyryl-cA MP, fors kolin and rolipram increase the level of intracellular cyclic adenosine monophosphate (CAMP), which results in an induction of the specific NEP activity without any effect on the specific ACE activity. Green tea extract was also able to increase the level of intracellular CAMP in vitro. These results demonstrate that the enhancement effect of the specific NEP activity, by green tea extract and its natural products, was selective and correlated with an elevated level of CAMP.