Редактирование: CTSD

Cathepsin D precursor (EC 3.4.23.5) [Contains: Cathepsin D light chain; Cathepsin D heavy chain] [CPSD]

==Publications==

{{medline-entry
|title=Myocardial cathepsin D is downregulated in sudden cardiac death.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32176724
|abstract=Cathepsins are the major lysosomal proteases that maintain intracellular homeostasis. Herein, we investigated the alterations in myocardial cathepsin expression during aging, cardiac hypertrophy, and sudden cardiac death ([[SCD]]). Cardiac tissue and blood were sampled from autopsy cases. Subjects were classified into three groups: [[SCD]] with cardiac hypertrophy (SCH), compensated cardiac hypertrophy (CCH), and control. Immunoblotting was performed for the major cardiac cathepsins and their targets: cathepsin B, D, and L ([[CTSB]]/D/L), p62, ATP synthase subunit c (ATPSC), and α-synuclein (ASNC). Immunohistochemical analysis and ELISA using serum samples were performed for [[CTSD]]. Cardiac [[CTSB]] and [[CTSD]] were upregulated with age (r = 0.63 and 0.60, respectively), whereas the levels of [[CTSL]], p62, ATPSC, and ASNC remained unchanged. In age-matched groups, cardiac [[CTSD]] was significantly downregulated in SCH (p = 0.006) and [[CTSL]] was moderately downregulated in CCH (p = 0.021); however, p62, ATPSC, and ASNC were not upregulated in cardiac hypertrophy. Immunohistochemistry also revealed decreased myocardial [[CTSD]] levels in SCH, and serum [[CTSD]] levels were relatively lower in SCH cases. Overall, these results suggest that upregulation of cardiac [[CTSB]] and [[CTSD]] with age may compensate for the elevated proteolytic demand, and that downregulation of [[CTSD]] is potentially linked to SCH.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Cathepsin D
* Death, Sudden, Cardiac
* Down-Regulation
* Female
* Humans
* Male
* Middle Aged
* Myocardium
* Substrate Specificity

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075574
}}
{{medline-entry
|title=[[SQSTM1]]/p62 and [[PPARGC1A]]/PGC-1alpha at the interface of autophagy and vascular senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31441382
|abstract=Defective macroautophagy/autophagy and mitochondrial dysfunction are known to stimulate senescence. The mitochondrial regulator [[PPARGC1A]] (peroxisome proliferator activated receptor gamma, coactivator 1 alpha) regulates mitochondrial biogenesis, reducing senescence of vascular smooth muscle cells (VSMCs); however, it is unknown whether autophagy mediates [[PPARGC1A]]-protective effects on senescence. Using [i]ppargc1a [/i] VSMCs, we identified the autophagy receptor [[SQSTM1]]/p62 (sequestosome 1) as a major regulator of autophagy and senescence of VSMCs. Abnormal autophagosomes were observed in VSMCs in aortas of [i]ppargc1a [/i] mice. [i]ppargc1a [/i] VSMCs in culture presented reductions in LC3-II levels; in autophagosome number; and in the expression of [[SQSTM1]] (protein and mRNA), [[LAMP2]] (lysosomal-associated membrane protein 2), [[CTSD]] (cathepsin D), and [[TFRC]] (transferrin receptor). Reduced [[SQSTM1]] protein expression was also observed in aortas of [i]ppargc1a [/i] mice and was upregulated by [[PPARGC1A]] overexpression, suggesting that [[SQSTM1]] is a direct target of [[PPARGC1A]]. Inhibition of autophagy by 3-MA (3 methyladenine), spautin-1 or [i]Atg5[/i] (autophagy related 5) siRNA stimulated senescence. Rapamycin rescued the effect of [i]Atg5[/i] siRNA in [i]Ppargc1a [/i] , but not in [i]ppargc1a [/i] VSMCs, suggesting that other targets of [[MTOR]] (mechanistic target of rapamycin kinase), in addition to autophagy, also contribute to senescence. [i]Sqstm1[/i] siRNA increased senescence basally and in response to [[AGT]] II (angiotensin II) and zinc overload, two known inducers of senescence. Furthermore, [i]Sqstm1 [/i]gene deficiency mimicked the phenotype of [i]Ppargc1a[/i] depletion by presenting reduced autophagy and increased senescence [i]in vitro[/i] and [i]in vivo[/i]. Thus, [[PPARGC1A]] upregulates autophagy reducing senescence by a [[SQSTM1]]-dependent mechanism. We propose [[SQSTM1]] as a novel target in therapeutic interventions reducing senescence. 3-MA: 3 methyladenine; ACTA2/SM-actin: actin, alpha 2, smooth muscle, aorta; ACTB/β-actin: actin beta; [[AGT]] II: angiotensin II; ATG5: autophagy related 5; BECN1: beclin 1; CAT: catalase; CDKN1A: cyclin-dependent kinase inhibitor 1A (P21); Chl: chloroquine; [[CTSD]]: cathepsin D; CYCS: cytochrome C, somatic; DHE: dihydroethidium; DPBS: Dulbecco's phosphate-buffered saline; EL: elastic lamina; EM: extracellular matrix; FDG: fluorescein-di-β-D-galactopyranoside; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; γH2AFX: phosphorylated H2A histone family, member X, H DCFDA: 2',7'-dichlorodihydrofluorescein diacetate; [[LAMP2]]: lysosomal-associated membrane protein 2; MASMs: mouse vascular smooth muscle cells; MEF: mouse embryonic fibroblast; [[NBR1]]: [[NBR1]], autophagy cargo receptor; NFKB/NF-κB: nuclear factor of kappa light polypeptide gene enhancer in B cells; [[MTOR]]: mechanistic target of rapamycin kinase; NFE2L2: nuclear factor, erythroid derived 2, like 2; NOX1: NADPH oxidase 1; OPTN: optineurin; PFA: paraformaldehyde; PFU: plaque-forming units; [[PPARGC1A]]/PGC-1α: peroxisome proliferator activated receptor, gamma, coactivator 1 alpha; Ptdln3K: phosphatidylinositol 3-kinase; RASMs: rat vascular smooth muscle cells; ROS: reactive oxygen species; SA-GLB1/β-gal: senescence-associated galactosidase, beta 1; SASP: senescence-associated secretory phenotype; SIRT1: sirtuin 1; Spautin 1: specific and potent autophagy inhibitor 1; [[SQSTM1]]/p62: sequestosome 1; SOD: superoxide dismutase; TEM: transmission electron microscopy; TFEB: transcription factor EB; [[TFRC]]: transferrin receptor; TRP53/p53: transformation related protein 53; TUBG1: tubulin gamma 1; VSMCs: vascular smooth muscle cells; WT: wild type.

|keywords=* Aging
* SQSTM1
* autophagy
* oxidative stress
* senescence
* vascular biology
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469683
}}
{{medline-entry
|title=Serum levels of cathepsin D, sirtuin1, and endothelial nitric oxide synthase are correlatively reduced in elderly healthy people.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26462844
|abstract=Nowadays, cathepsins have been reported to be related to aging. The aim of this study is to evaluate the association between serum levels of cathepsin D ([[CTSD]]) and human aging. In the present study, we analyzed the serum levels of [[CTSD]] and its relation with levels of sirtuin1 ([[SIRT1]]) and endothelial nitric oxide synthase (eNOS) activity, which were known having an important role in aging. This study recruited 90 healthy subjects (62 men and 28 women), which were subdivided into three groups with respect to age: young (about 19 years old, n = 30), middle-age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of [[CTSD]] and [[SIRT1]] were measured by enzyme-linked immunosorbent assay, and eNOS activity was assessed by the conversion of 14(C)-L-arginine to 14(C)-L-citrulline. Elderly subjects had significantly lower [[CTSD]], [[SIRT1]], and eNOS than younger ones. Serum levels of [[CTSD]] were negatively correlated with age. There was a statistically significant positive correlation between serum levels of [[CTSD]], eNOS, and [[SIRT1]]. This study shows lower serum [[CTSD]] values in elderly subjects than in younger subjects. This is the first to demonstrate age-related changes in cathepsin D levels in humans and the association between [[SIRT1]] and eNOS.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Cathepsin D
* Female
* Humans
* Male
* Middle Aged
* Nitric Oxide Synthase Type III
* Sirtuin 1
* Young Adult
|keywords=* Aging
* Cathepsin D
* SIRT1
* eNOS
|full-text-url=https://sci-hub.do/10.1007/s40520-015-0472-7
}}
{{medline-entry
|title=Differentially abundant transcripts in PBMC of hospitalized geriatric patients with hip fracture compared to healthy aged controls.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21074600
|abstract=The abundance of a selection of transcript species involved in inflammation, immunosenescence and stress response was compared between PBMC of 35 geriatric patients with hip fracture in acute phase (days 2-4 after hospitalization) or convalescence phase (days 7-10) and 28 healthy aged controls. Twenty-nine differentially abundant transcripts were identified in acute phase versus healthy ageing. Twelve of these transcripts remained differentially abundant in convalescence phase, and 22 were similarly differentially abundant in acute phase of geriatric infectious diseases. Seven of these 22 transcripts were previously identified as differentially abundant in PBMC of healthy aged versus healthy young controls, with further alteration for [[CD28]], [[CD69]], [[LCK]], [[CTSD]], [[HMOX1]], and [[TNFRSF1A]] in acute phase after geriatric hip fracture and infectious diseases. The next question is whether these alterations are common to other geriatric diseases and/or preexist before the clinical onset of the diseases.
|mesh-terms=* Acute-Phase Reaction
* Adult
* Aged
* Aged, 80 and over
* Aging
* Antigens, CD
* Antigens, Differentiation, T-Lymphocyte
* Base Sequence
* CD28 Antigens
* Case-Control Studies
* Cathepsin D
* DNA Primers
* Female
* Gene Expression Profiling
* Heme Oxygenase-1
* Hip Fractures
* Hospitalization
* Humans
* Lectins, C-Type
* Leukocytes, Mononuclear
* Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
* Male
* Receptors, Tumor Necrosis Factor, Type I

|full-text-url=https://sci-hub.do/10.1016/j.exger.2010.10.012
}}
{{medline-entry
|title=Influence and interactions of cathepsin D, [[HLA-DRB1]] and [[APOE]] on cognitive abilities in an older non-demented population.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16417614
|abstract=Cathepsin D ([[CTSD]]), human leukocyte antigen DRB1 ([[HLA-DRB1]]) and apolipoprotein E ([[APOE]]) have all been associated with cognitive ability in both demented and non-demented individuals. [[CTSD]] is a pleiotrophic protein whose functions include the processing of proteins prior to presentation by HLA. Several studies have also reported that a functional exon 2 polymorphism in the [[CTSD]] gene interacts with [[APOE]]epsilon4 resulting in an increased risk of developing Alzheimer's disease (AD). We have previously reported that the [[CTSD]] exon 2 polymorphism regulates fluid intelligence. In this study, we extend this finding to other cognitive domains and investigate interactions with [[APOE]] and [[HLA-DRB1]]. Using a cohort of 766 non-demented volunteers, we found that the [[CTSD]] exon 2 T allele was associated with a decrease in several cognitive domains that comprise processing speed [random letters (RLs) test, P = 0.012; alphabet-coding task (ACT), P = 0.001], spatial recall (SR) (P = 0.016) and an additional test of fluid intelligence (P = 0.010). We also observed that the HLA-[[DR1]] was associated with enhanced cumulative recall ability (P = 0.006), and conversely HLA-DR5 was associated with diminished delayed verbal recall and SR abilities (P = 0.014 and P = 0.003, respectively). When analysed independently, [[APOE]]epsilon4 did not influence any cognitive domains. In contrast, [[CTSD]] T/[[APOE]]epsilon4-positive volunteers scored lower on tests of fluid intelligence (P = 0.015), processing speed (ACT, P = 0.001; RL, P = 0.013) and immediate recall (P = 0.029). Scores were lower for all these tests than when [[CTSD]] and [[APOE]] were analysed independently. This supports previous findings in AD that have also reported an epistatic interaction. In addition, we found that [[CTSD]] T/HLA-DR2-positive volunteers had reduced processing speed (ACT, P = 0.040; RL, P = 0.014) and had significantly lower cumulative and SR abilities (P = 0.003 and P = 0.001, respectively). Biological interaction between these two proteins has previously been shown where HLA-DR2 binds more readily to the myelin basic protein ([[MBP]]) compared with other DR antigens, preventing [[MBP]] cleavage by [[CTSD]].
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Apolipoprotein E4
* Apolipoproteins E
* Cathepsin D
* Cognition
* Cross-Sectional Studies
* Female
* Gene Frequency
* Genotype
* HLA-DR Antigens
* HLA-DRB1 Chains
* Humans
* Male
* Memory
* Mental Processes
* Middle Aged
* Polymorphism, Genetic
* Reference Values
* Regression Analysis

|full-text-url=https://sci-hub.do/10.1111/j.1601-183X.2006.00191.x
}}
{{medline-entry
|title=Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12556904
|abstract=General intelligence is a heritable trait that is a risk factor for both the onset of dementia and the rate of cognitive decline in community-dwelling older persons. Previous studies screening for quantitative trait loci (QTLs) that influence general intelligence in healthy individuals have identified four loci, two of which are located within the genes insulin-like growth factor 2 receptor ([[IGF2R]]) and the Msx1 homeobox. Here, we report the finding of another QTL associated with general intelligence that is located within exon 2 of the cathepsin D ([[CTSD]]) gene. A group of 767 healthy adults with a follow-up period of over 15 years have been analyzed for cross-sectional and longitudinal trends in cognitive change using the Heim intelligence test score (AH4-1). We observed a significant association (P = 0.01) between a functional C > T (Ala > Val) transition within exon 2 of the [[CTSD]] gene that increases the secretion of pro-[[CTSD]] from the cell, and the AH4-1 score at initial testing on entry to the longitudinal study. Interestingly, [[CTSD]] is transported by [[IGF2R]] from the trans Golgi network to the lysosome.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Cathepsin D
* Cognition
* Cognition Disorders
* Exons
* Female
* Genotype
* Humans
* Intelligence
* Male
* Middle Aged
* Polymorphism, Genetic

|full-text-url=https://sci-hub.do/10.1038/sj.mp.4001239
}}