Regulation of human and mouse procathepsin E gene expression

Cook, Matthew; Caswell, Richard; Richards, Roy J.; Kay, John; Tatnell, Peter J.

doi:10.1046/j.1432-1327.2001.02159.x

Cited by 27 publications

(28 citation statements)

References 45 publications

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“…Moreover, the fact that cathepsin E is hardly detected in adipocytes but is highly 8 expressed in macrophages further supports our notion. In fact, Cook et al [14] reported that the mRNA level of cathepsin E was completely undetectable in 3T3-L1 cells, which is a useful cell line for adipocyte differentiation. In this study, the number of F4/80-positive cells in CatE -/-WAT was significantly lower than that in wild-type WAT, indicating reduced macrophage infiltration in CatE -/-WAT.…”

Section: Discussionmentioning

confidence: 99%

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Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet

Kadowaki

Kido

Hatakeyama

et al. 2014

Biochemical and Biophysical Research Communications

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Running title: Fat-induced cathepsin E-deficient mice Key words: cathepsin E, high-fat diet, adipose tissue AbstractCathepsin E is an intracellular aspartic proteinase, which is predominantly distributed in immune-related and epithelial cells. However, the role of the enzyme in adipose tissues remains unknown. In this study, we investigated the characteristics of cathepsin E-deficient (CatE -/-) mice fed a high-fat diet (HFD), as a mouse model of obesity. HFD-fed CatE -/-mice displayed reduced body weight gain and defective development of white adipose tissue (WAT) and brown adipose tissue (BAT), compared with HFD-fed wild-type mice. Moreover, fat-induced CatE -/-mice showed abnormal lipid accumulation in non-adipose tissues characterized by hepatomegaly, which is probably due to defective adipose tissue development. Detailed pathological and biochemical analyses showed that hepatomegaly was accompanied by hepatic steatosis and hypercholesterolemia in HFD-induced CatE -/-mice. In fat-induced CatE -/-mice, the number of macrophages infiltrating into WAT was significantly lower than in fat-induced wild-type mice. Thus, the impaired adipose tissue development in HFD-induced CatE -/-mice was probably due to reduced infiltration of macrophages and may lead to hepatomegaly accompanied by hepatic steatosis and hypercholesterolemia.

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Section: Discussionmentioning

confidence: 99%

“…Several lines of evidence indicate that cathepsin E is hardly detectable in pre-adipocyte cells [14].…”

Section: Impaired Development Of Adipose Tissues and Reduced Macrophamentioning

confidence: 99%

Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet

Kadowaki

Kido

Hatakeyama

et al. 2014

Biochemical and Biophysical Research Communications

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“…Cathepsin E is an intracellular aspartic protease homologous to cathepsin D [22,35]. Cathepsin D is localized within the lysosomes of most cells [9] while cathepsin E is localized in various non-lysosomal compartments such as the endosome, the endoplasmic reticulum and the Golgi complex and has a limited cell and tissue distribution [26,35,37,41]. Cathepsin E has been detected in mouse, rabbit and rat macrophages [2,9,30,36].…”

Section: Discussionmentioning

confidence: 99%

Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages

2008

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-Porcine reproductive and respiratory syndrome virus (PRRSV) replicates in differentiated macrophages. In macrophages, heparan sulphate glycosaminoglycans mediate the initial PRRSV attachment and the receptor sialoadhesin mediates both PRRSV attachment and internalization into endosomes. Upon a pH drop, PRRSV is uncoated and its genome is released from the endosomes into the cytoplasm, which allows virus replication. However, expression of heparan sulphate and sialoadhesin in non-susceptible cells only allows virus internalization, but no virus uncoating and infection, indicating that other factors are involved. In the present study, it is shown that treatment of macrophages with serum (mainly the alpha-globulin fraction) inhibited PRRSV infection without affecting attachment and internalization. Because alpha-globulins contain several protease inhibitors, macrophages were treated with different protease inhibitors to investigate the involvement of proteases in PRRSV uncoating. Treatment of macrophages with broadly active inhibitors of serine or aspartic proteases, but not cysteine-or metallo-proteases, inhibited PRRSV uncoating and infection. Further investigation using specific inhibitors indicated that the aspartic protease cathepsin E is involved during PRRSV uncoating, but did not allow identification of the serine protease involved. The involvement of cathepsin E during PRRSV uncoating was confirmed by partial co-localization of internalized PRRSV with cathepsin E. Furthermore, cathepsin E expression increased with macrophage cultivation, which was positively correlated with an increased susceptibility to PRRSV infection. Together, these data show that, in macrophages, both the aspartic protease cathepsin E and an unidentified trypsin-like serine protease are involved in uncoating of internalized PRRSV and subsequent infection. porcine arterivirus / macrophage / virus entry / protease / receptor

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“…There are also reports of lower levels of expression in the rat liver, particularly in the bile canaliculi and microvilli [2,14]. Previous studies of CTSE transcriptional regulation indicated that CTSE was positively regulated by several cell-type specific transcription factors, including GATA-1, erythroid specific, PU.1, pancreatic, and Isl1, hematopoietic [14]. A ubiquitously expressed transcription factor, YY1, was reported as a negative regulator of CTSE promoter activity [14].…”

mentioning

confidence: 99%

“…Previous studies of CTSE transcriptional regulation indicated that CTSE was positively regulated by several cell-type specific transcription factors, including GATA-1, erythroid specific, PU.1, pancreatic, and Isl1, hematopoietic [14]. A ubiquitously expressed transcription factor, YY1, was reported as a negative regulator of CTSE promoter activity [14]. Later, other studies revealed that the transcription factor CIITA, specific to dendritic and B cells, also negatively regulates the expression of CTSE [30].…”

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confidence: 99%

Regulation of the human cathepsin E gene by the constitutive androstane receptor

Page

Strom

Omiecinski

2007

Archives of Biochemistry and Biophysics

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Cathepsin E (CTSE) is an aspartic protease that has been linked to antigen processing and innate immunity. Elevated levels of CTSE expression have also been associated with several forms of cancer, including carcinomas exhibiting highly invasive character. In this study, we performed DNA microarray experiments, together with quantitative reverse transcriptase PCR analyses and enzymatic activity determinations to identify human CTSE as a novel target gene for regulation by the constitutive androstane receptor (CAR), a nuclear receptor activated by the liver tumor promoting agent, phenobarbital. In particular, two motifs within the 5′-flanking region of the human CTSE gene were identified as direct sites of interaction with CAR/RXRα heterodimers, a direct repeat-3 site at position −766 and a direct repeat-4 site at position −1407. Thus, these studies demonstrate CAR-mediated regulation of CTSE within primary hepatocyte cultures from several individual donors and suggest that elevated CTSE activity may play a functional role in the etiology of hepatocarcinogenesis. KeywordsCathepsin E; Constitutive androstane receptor; Hepatocytes; Primary hepatocytes; Liver; Human; Hepatocytes Cathepsin E (CTSE) 1 is an intracellular aspartic protease that hydrolyzes various biologically active peptides [1]. Unlike related proteases, CTSE is localized outside of the lysosomal system and likely functions in extralysosomal proteolysis [2]. Although its exact biological functions remain elusive, several physiological roles of CTSE have been reported, including roles in immune defense and antigen processing [3][4][5]. In this respect, CTSEdeficient mice exhibit markedly increased susceptibility to both gram positive and gram negative bacterial infection, likely due to impaired regulation of bacterial elimination [5]. Given the apparent association of enhanced CTSE expression with hepatocellular carcinoma, we hypothesize that liver tumor promoting agents may function to enhance CTSE expression levels in liver and that increased proteolytic activity may underlie certain mechanistic aspects of the tumor promotion process. In the studies reported here, we identify CTSE expression in human hepatoctyes. In particular, microarray expression profiling analyses indicated that exposures to the classical liver tumor promoter, phenobarbital (PB), resulted in increased CTSE transcript levels within primary hepatocyte cultures from several individual donors, a result that was confirmed by quantitative RT-PCR experiments. Further, we demonstrate that the constitutive androstane receptor (CAR) acts as a transcriptional regulator of the human CTSE gene and that these events lead to PB-inducible increases in functional hepatic CTSE enzymatic activity. Materials and methods ChemicalsPhenobarbital sodium salt was obtained from UWMC Drug Services (Seattle, WA). Clotrimazole, meclizine and dimethyl sulfoxide (DMSO) were purchased from Sigma (St. Louis, MO). CITCO was purchased from BIOMOL Research Laboratories (Plymouth Meeting, PA). Cell cultureCO...

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Regulation of human and mouse procathepsin E gene expression

Cited by 27 publications

References 45 publications

Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet

Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet

Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages

Regulation of the human cathepsin E gene by the constitutive androstane receptor

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