Topic
ACAT1
About: ACAT1 is a research topic. Over the lifetime, 19 publications have been published within this topic receiving 387 citations. The topic is also known as: ACAT & MAT.
Papers
TL;DR: The marked alterations in cholesterol homeostasis indicate that selectively inhibiting ACAT1 in the setting of severe hyperlipidemia may have detrimental consequences.
Abstract: Inhibitors of acyl CoA:cholesterol acyltransferase (ACAT) have attracted considerable interest as a potential treatment for atherosclerosis. Currently available inhibitors probably act nonselectively against the two known ACATs. One of these enzymes, ACAT1, is highly expressed in macrophages in atherosclerotic lesions, where it contributes to foam-cell formation. In this study, we examined the effects of selective ACAT1 deficiency in two mouse models of atherosclerosis. In the setting of severe hypercholesterolemia caused by deficiency in apoE or the LDL receptor (LDLR), total ACAT1 deficiency led to marked alterations in cholesterol homeostasis and extensive deposition of unesterified cholesterol in the skin and brain. Bone marrow transplantation experiments demonstrated that ACAT1 deficiency in macrophages was sufficient to cause dermal xanthomas in hyperlipidemic LDLR-deficient mice. ACAT1 deficiency did not prevent the development of atherosclerotic lesions in either apoE-deficient or LDLR-deficient mice, despite causing relatively lower serum cholesterol levels. However, the lesions in ACAT1-deficient mice were atypical in composition, with reduced amounts of neutral lipids and a paucity of macrophages in advanced lesions. Although the latter findings may be associated with increased lesion stability, the marked alterations in cholesterol homeostasis indicate that selectively inhibiting ACAT1 in the setting of severe hyperlipidemia may have detrimental consequences.
241 citations
TL;DR: The recent findings, which unexpectedly expand the known functions of ACAT1, indicating a role for ACat1 well beyond its classical activity, point to AC AT1 as a potential new anti-cancer target.
84 citations
TL;DR: Avasimibe complements the efficacy of a multi-peptide Kras vaccine in controlling lung cancer development and growth and enhanced the effectiveness of Kras vaccines target mutant Kras.
43 citations
TL;DR: A dose-dependent increase of ACat2 mRNA expression, an increased enzymatic activity of ACAT2, and increased esterified cholesterol mass upon cholesterol loading are shown, suggesting that human ACAT 2 is transcriptionally regulated by cholesterol.
29 citations
TL;DR: It is proposed that all one‐base substitutions at the initiator methionine codon in the T2 gene could be mutations, which retain some residual T2 activity.
Abstract: Initiator codon mutations are relatively uncommon and less well characterized compared to other types of mutations. We identified a novel initiator codon mutation (c.2T>C) heterozygously in a Japanese patient (Patient GK30) with mitochondrial acetoacetyl-CoA thiolase (T2) gene deficiency (ACAT1 deficiency); c.149delC was on the other allele. We examined translation efficiencies of nine mutant T2 cDNAs harboring one-base substitutions at the initiator methionine codon using in vivo transient expression analysis. We found that all the mutants produced wild-type T2 polypeptide, to various degrees (wild type (100%) > c.1A>C (66%) > c.2T>C, c.3G>C, c.3G>T (22%) > c3G>A, c.1A>G (11%) > c.2T>A, c.2T>G, c.1A>T (7.4%)). T2 mRNA expression levels in Patient GK08 (a homozygote of c.2T>A) and Patient GK30 fibroblasts, respectively, were almost the same as in control fibroblasts, when examined using semiquantitative PCR. This means that initiator codon mutations did not affect T2 mRNA levels. We propose that all one-base substitutions at the initiator methionine codon in the T2 gene could be mutations, which retain some residual T2 activity. Hum Mutat 21:587–592, 2003. © 2003 Wiley-Liss, Inc.
24 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2020 | 3 |
| 2019 | 4 |
| 2017 | 5 |
| 2016 | 1 |
| 2014 | 1 |
| 2008 | 2 |