α(1B)-Adrenoceptor signaling molecule expression in Alzheimer's disease brain tissue

초록

Objective: G alpha(h) (tissue transglutaminase; TGII), known as the alpha(1B)-adrenoceptor signal mediator, is a bifunctional enzyme possessing transglutaminase and guanosine triphosphatase activities. The microtubule-associated protein tau plays a role in formation of neurofibrillary tangles in Alzheimer's disease (AD) brain. Tau is also known as a substrate of transglutaminase. We aimed to better understand the correlation between alpha(1B)-adrenoceptor signaling and AD. Methods: We examined not only the cross-linking ability of TGII for tau, but also the expression level of tau as well as alpha(1B)-adrenoceptor signaling molecules, TGII and phospholipase C-delta 1, in the human brain. Results: When the tau protein was assayed as a transglutaminase substrate of TGII, tau proteins formed cross-linked products. However, phospholipase C-delta 1 inhibited transglutaminase activity in TGII to cross-link with tau in vitro. The amount of expressed mRNA in AD brain tissue was elevated 2 similar to 10 fold for tau and 3 similar to 20 fold for TGII. Consistent with these observations, the densities of expressed proteins in AD brain tissue also increased 9 fold for tau and 15 fold for TGII. Moreover, phospholipase C-delta 1, which is a negative regulator for transglutaminase activity of TGII, also increased 2 similar to 25 fold for mRNA as well as 8 fold for protein in AD brain tissue. In contrast, expressed mRNA and protein activity for alpha(1B)-adrenoceptor were almost the same between AD and normal brains. Conclusion: These results suggest that the alpha(1B)-adrenoceptor signal mediator, TGII and tau, as a substrate of TGII might have a pathophysiological role in AD, but this correlation may be independent of the alpha(1B)-adrenoceptor signaling system, including alpha(1B)-adrenoceptor and phospholipase C-delta 1.

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