The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor protein.

Allinson, Tobias M. J. and Parkin, Edward T. and Condon, Thomas P. and Schwager, Sylva L. U. and Sturrock, Edward D. and Turner, Anthony J. and Hooper, Nigel M. (2004) The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor protein. European Journal of Biochemistry, 271 (12). pp. 2539-2547. ISSN 0014-2956

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Abstract

Numerous transmembrane proteins, including the blood pressure regulating angiotensin converting enzyme (ACE) and the Alzheimer's disease amyloid precursor protein (APP), are proteolytically shed from the plasma membrane by metalloproteases. We have used an antisense oligonucleotide (ASO) approach to delineate the role of ADAM10 and tumour necrosis factor-α converting enzyme (TACE; ADAM17) in the ectodomain shedding of ACE and APP from human SH-SY5Y cells. Although the ADAM10 ASO and TACE ASO significantly reduced (> 81%) their respective mRNA levels and reduced the α-secretase shedding of APP by 60% and 30%, respectively, neither ASO reduced the shedding of ACE. The mercurial compound 4-aminophenylmercuric acetate (APMA) stimulated the shedding of ACE but not of APP. The APMA-stimulated secretase cleaved ACE at the same Arg-Ser bond in the juxtamembrane stalk as the constitutive secretase but was more sensitive to inhibition by a hydroxamate-based compound. The APMA-activated shedding of ACE was not reduced by the ADAM10 or TACE ASOs. These results indicate that neither ADAM10 nor TACE are involved in the shedding of ACE and that APMA, which activates a distinct ACE secretase, is the first pharmacological agent to distinguish between the shedding of ACE and APP.

Item Type:
Journal Article
Journal or Publication Title:
European Journal of Biochemistry
Uncontrolled Keywords:
/dk/atira/pure/researchoutput/libraryofcongress/qh301
Subjects:
?? BIOCHEMISTRYQH301 BIOLOGY ??
ID Code:
9449
Deposited By:
Deposited On:
11 Jun 2008 10:04
Refereed?:
Yes
Published?:
Published
Last Modified:
22 Sep 2023 00:10