Molecular studies define the primary structure of α1-antichymotrypsin (ACT) protease inhibitor in Alzheimer's disease brains. Comparison of act in hippocampus and liver

Shin Rong Hwang, Brent Steineckert, Andrea Kohn, M. Palkóvits, Vivian Y H Hook

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

An α1-antichymotrypsin-like serpin has been implicated in Alzheimer's disease (AD) based on immunochemical detection of α1-antichymotrypsin (ACT) in amyloid plaques from the hippocampus of AD brains. The presence of neuroendocrine isoforms of ACTs and reported variations in human liver ACT cDNA sequences raise the question of the molecular identity of ACT in brain. In this study, direct reverse transcription-polymerase chain reaction and cDNA sequencing indicate that the hippocampus ACT possesses the reactive site loop that is characteristic of serpins, with Leu as the predicted P1 residue interacting with putative chymotrypsin-like target proteases. The deduced primary sequence of the human hippocampus ACT possesses more than 90% homology with reported primary sequences for the human liver ACT. Moreover, identical ACT primary sequences deduced from the cDNAs were demonstrated in the hippocampus of control and AD brains. Northern blots showed that ACT mRNA expression in hippocampus was 900 times lower than that in liver. Also, hippocampus and liver ACT proteins demonstrated differential sensitivities to deglycosylation. Overall, reverse transcription-polymerase chain reaction combined with cDNA and primary sequence analyses have defined the molecular identity of human hippocampus ACT in control and AD brains. The determined reactive site loop domain of hippocampus ACT will allow prediction of potential target proteases inhibited by ACT in AD.

Original languageEnglish
Pages (from-to)1821-1827
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number3
DOIs
Publication statusPublished - Jan 15 1999

Fingerprint

Protease Inhibitors
Liver
Hippocampus
Brain
Alzheimer Disease
Complementary DNA
Serpins
Polymerase chain reaction
Transcription
Peptide Hydrolases
Reverse Transcription
Chymotrypsin
Catalytic Domain
Amyloid
Chymases
Protein Isoforms
Polymerase Chain Reaction
Amyloid Plaques
Messenger RNA
Northern Blotting

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular studies define the primary structure of α1-antichymotrypsin (ACT) protease inhibitor in Alzheimer's disease brains. Comparison of act in hippocampus and liver. / Hwang, Shin Rong; Steineckert, Brent; Kohn, Andrea; Palkóvits, M.; Hook, Vivian Y H.

In: Journal of Biological Chemistry, Vol. 274, No. 3, 15.01.1999, p. 1821-1827.

Research output: Contribution to journalArticle

@article{2c0a1a881eeb4d1b9cd0306cf3799d64,
title = "Molecular studies define the primary structure of α1-antichymotrypsin (ACT) protease inhibitor in Alzheimer's disease brains. Comparison of act in hippocampus and liver",
abstract = "An α1-antichymotrypsin-like serpin has been implicated in Alzheimer's disease (AD) based on immunochemical detection of α1-antichymotrypsin (ACT) in amyloid plaques from the hippocampus of AD brains. The presence of neuroendocrine isoforms of ACTs and reported variations in human liver ACT cDNA sequences raise the question of the molecular identity of ACT in brain. In this study, direct reverse transcription-polymerase chain reaction and cDNA sequencing indicate that the hippocampus ACT possesses the reactive site loop that is characteristic of serpins, with Leu as the predicted P1 residue interacting with putative chymotrypsin-like target proteases. The deduced primary sequence of the human hippocampus ACT possesses more than 90{\%} homology with reported primary sequences for the human liver ACT. Moreover, identical ACT primary sequences deduced from the cDNAs were demonstrated in the hippocampus of control and AD brains. Northern blots showed that ACT mRNA expression in hippocampus was 900 times lower than that in liver. Also, hippocampus and liver ACT proteins demonstrated differential sensitivities to deglycosylation. Overall, reverse transcription-polymerase chain reaction combined with cDNA and primary sequence analyses have defined the molecular identity of human hippocampus ACT in control and AD brains. The determined reactive site loop domain of hippocampus ACT will allow prediction of potential target proteases inhibited by ACT in AD.",
author = "Hwang, {Shin Rong} and Brent Steineckert and Andrea Kohn and M. Palk{\'o}vits and Hook, {Vivian Y H}",
year = "1999",
month = "1",
day = "15",
doi = "10.1074/jbc.274.3.1821",
language = "English",
volume = "274",
pages = "1821--1827",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - Molecular studies define the primary structure of α1-antichymotrypsin (ACT) protease inhibitor in Alzheimer's disease brains. Comparison of act in hippocampus and liver

AU - Hwang, Shin Rong

AU - Steineckert, Brent

AU - Kohn, Andrea

AU - Palkóvits, M.

AU - Hook, Vivian Y H

PY - 1999/1/15

Y1 - 1999/1/15

N2 - An α1-antichymotrypsin-like serpin has been implicated in Alzheimer's disease (AD) based on immunochemical detection of α1-antichymotrypsin (ACT) in amyloid plaques from the hippocampus of AD brains. The presence of neuroendocrine isoforms of ACTs and reported variations in human liver ACT cDNA sequences raise the question of the molecular identity of ACT in brain. In this study, direct reverse transcription-polymerase chain reaction and cDNA sequencing indicate that the hippocampus ACT possesses the reactive site loop that is characteristic of serpins, with Leu as the predicted P1 residue interacting with putative chymotrypsin-like target proteases. The deduced primary sequence of the human hippocampus ACT possesses more than 90% homology with reported primary sequences for the human liver ACT. Moreover, identical ACT primary sequences deduced from the cDNAs were demonstrated in the hippocampus of control and AD brains. Northern blots showed that ACT mRNA expression in hippocampus was 900 times lower than that in liver. Also, hippocampus and liver ACT proteins demonstrated differential sensitivities to deglycosylation. Overall, reverse transcription-polymerase chain reaction combined with cDNA and primary sequence analyses have defined the molecular identity of human hippocampus ACT in control and AD brains. The determined reactive site loop domain of hippocampus ACT will allow prediction of potential target proteases inhibited by ACT in AD.

AB - An α1-antichymotrypsin-like serpin has been implicated in Alzheimer's disease (AD) based on immunochemical detection of α1-antichymotrypsin (ACT) in amyloid plaques from the hippocampus of AD brains. The presence of neuroendocrine isoforms of ACTs and reported variations in human liver ACT cDNA sequences raise the question of the molecular identity of ACT in brain. In this study, direct reverse transcription-polymerase chain reaction and cDNA sequencing indicate that the hippocampus ACT possesses the reactive site loop that is characteristic of serpins, with Leu as the predicted P1 residue interacting with putative chymotrypsin-like target proteases. The deduced primary sequence of the human hippocampus ACT possesses more than 90% homology with reported primary sequences for the human liver ACT. Moreover, identical ACT primary sequences deduced from the cDNAs were demonstrated in the hippocampus of control and AD brains. Northern blots showed that ACT mRNA expression in hippocampus was 900 times lower than that in liver. Also, hippocampus and liver ACT proteins demonstrated differential sensitivities to deglycosylation. Overall, reverse transcription-polymerase chain reaction combined with cDNA and primary sequence analyses have defined the molecular identity of human hippocampus ACT in control and AD brains. The determined reactive site loop domain of hippocampus ACT will allow prediction of potential target proteases inhibited by ACT in AD.

UR - http://www.scopus.com/inward/record.url?scp=0033555611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033555611&partnerID=8YFLogxK

U2 - 10.1074/jbc.274.3.1821

DO - 10.1074/jbc.274.3.1821

M3 - Article

C2 - 9880565

AN - SCOPUS:0033555611

VL - 274

SP - 1821

EP - 1827

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 3

ER -