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Gene Review

Ctsd  -  cathepsin D

Rattus norvegicus

Synonyms: Cathepsin D
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Disease relevance of Ctsd


Psychiatry related information on Ctsd


High impact information on Ctsd


Chemical compound and disease context of Ctsd

  • Enzyme activity was maximal at pH 3.0-3.5 and inhibited more than 90% by pepstatin (6.7 micrograms/ml), suggesting that the enzyme is cathepsin D. In subsequent experiments we measured cathepsin D-like activity in cortex, tubules and glomeruli isolated from rats with puromycin aminonucleoside (PAN)-induced nephrotic syndrome [13].
  • Administration of exogenous testosterone in varying doses to castrated rats prevented or retarded prostatic weight loss as well as the increase in cathepsin D activity in a dose related manner [14].
  • Treatment with CGS-16617 (1 microgram/kg) or CGS-13080 (200 micrograms/kg) alone did not alter significantly postoligemic hypotension or the increase in plasma cathepsin D activity in shocked rats, compared with hemorrhaged rats receiving only their vehicle [15].
  • In this study, we demonstrate, for the first time, immunohistochemical evidence that A beta and cathepsin D, a lysosomal enzyme, accumulate in vacuolated rat soleus muscle due to chloroquine-induced myopathy [16].
  • CV-6209 (1 mg/kg) also significantly attenuated the increase in plasma cathepsin D activity following hemorrhage compared with hemorrhaged rats receiving only its vehicle (i.e. 0.9% NaCl) [17].

Biological context of Ctsd

  • Given the documented role of cathepsin D (CatD) in apoptosis of other cell types, we hypothesized that CatD might be the AEC enzyme responsible for the conversion of angiotensinogen into ANG I, the substrate for ACE [18].
  • Down-regulation of cathepsin-D expression by antisense gene transfer inhibits tumor growth and experimental lung metastasis of human breast cancer cells [1].
  • To investigate the role of this protease in breast cancer growth and progression to metastasis, we stably transfected a highly metastatic human breast cancer cell line, MDA-MB-231, with a plasmid containing either the full-length cDNA for cathepsin-D or a 535 bp antisense cathepsin-D cDNA fragment [1].
  • In fact, the treatment with 0.1 micromol/L HNE accelerated the PKC-dependent transport of lysosomal procathepsin D from the trans-Golgi network to the endosomal-lysosomal compartment and, in addition, increased the exocytosis of mature cathepsin D (CD) from these compartments [19].
  • Antigen stimulation also induced exocytosis of immature CD forms accumulated by ammonium chloride, suggesting the existence of an intermediate station in the pathway for granule biogenesis still sensitive to regulated exocytosis [20].

Anatomical context of Ctsd


Associations of Ctsd with chemical compounds


Enzymatic interactions of Ctsd


Regulatory relationships of Ctsd

  • Our findings suggest the presence of mycobacterial hsp65 determinants that selectively trigger AA-regulating T cells and illustrate that cathepsin D may be used as an experimental tool to generate such determinants [28].
  • These results suggest that cathepsins B and D are involved in astrocytic apoptosis: cathepsin D acts as a death-inducing factor upstream of caspase-3 and the caspase-independent apoptosis is regulated antagonistically by cathepsins B and D [29].
  • The neutral proteinase and cathepsin B-like activity were inhibited by leupeptin and not by pepstatin while the converse obtained for cathepsin D activity [30].

Other interactions of Ctsd


Analytical, diagnostic and therapeutic context of Ctsd

  • The presence of procathepsin D, a zymogen of the soluble lysosomal aspartic proteinase cathepsin D, was detected in rat milk using Western blot analysis and assay of proteolytic activity in acidic buffers [36].
  • Confocal microscopy on brain sections revealed that this transporter colocalizes with cathepsin D, an established lysosomal marker [37].
  • Moreover, the elution profile of the endosomal acidic insulinase activity on a gel-filtration TSK-GEL G3000 SW(XL) high performance liquid chromatography column corresponded exactly with the elution profile of the immunoreactive 45-kDa mature form of endosomal CD [38].
  • Immunofluorescence studies showed a largely vesicular staining pattern for internalized insulin in rat hepatocytes that colocalized partially with CD [38].
  • Neither perfusion nor insulin had any effect on total cathepsin D activity [39].


  1. Down-regulation of cathepsin-D expression by antisense gene transfer inhibits tumor growth and experimental lung metastasis of human breast cancer cells. Glondu, M., Liaudet-Coopman, E., Derocq, D., Platet, N., Rochefort, H., Garcia, M. Oncogene (2002) [Pubmed]
  2. Hypoxia inhibits expression of prolactin and secretion of cathepsin-D by the GH4C1 pituitary adenoma cell line. Cosío, G., Jeziorski, M.C., López-Barrera, F., De La Escalera, G.M., Clapp, C. Lab. Invest. (2003) [Pubmed]
  3. Predictive value of cathepsin-D for cervical lymph node metastasis in head and neck squamous cell carcinoma. Gandour-Edwards, R., Trock, B., Donald, P.J. Head & neck. (1999) [Pubmed]
  4. Prognostic significance of the metastasis-inducing protein S100A4 (p9Ka) in human breast cancer. Rudland, P.S., Platt-Higgins, A., Renshaw, C., West, C.R., Winstanley, J.H., Robertson, L., Barraclough, R. Cancer Res. (2000) [Pubmed]
  5. Novel cathepsin D inhibitors block the formation of hyperphosphorylated tau fragments in hippocampus. Bi, X., Haque, T.S., Zhou, J., Skillman, A.G., Lin, B., Lee, C.E., Kuntz, I.D., Ellman, J.A., Lynch, G. J. Neurochem. (2000) [Pubmed]
  6. Increase in levels of polyubiquitin and proteasome mRNA in skeletal muscle during starvation and denervation atrophy. Medina, R., Wing, S.S., Goldberg, A.L. Biochem. J. (1995) [Pubmed]
  7. Effect of motor activity on cathepsin D activity in rat muscles. Górski, J., Worowski, K. Acta physiologica Polonica. (1982) [Pubmed]
  8. Mass isolation and culture of rat kupffer cells. Munthe-Kaas, A.C., Berg, T., Seglen, P.O., Seljelid, R. J. Exp. Med. (1975) [Pubmed]
  9. Sensitivity and protein turnover response to glucocorticoids are different in skeletal muscle from adult and old rats. Lack of regulation of the ubiquitin-proteasome proteolytic pathway in aging. Dardevet, D., Sornet, C., Taillandier, D., Savary, I., Attaix, D., Grizard, J. J. Clin. Invest. (1995) [Pubmed]
  10. Differential localization and functional role of calsequestrin in growing and differentiated myoblasts. Raichman, M., Panzeri, M.C., Clementi, E., Papazafiri, P., Eckley, M., Clegg, D.O., Villa, A., Meldolesi, J. J. Cell Biol. (1995) [Pubmed]
  11. The differential degradation of two cytosolic proteins as a tool to monitor autophagy in hepatocytes by immunocytochemistry. Rabouille, C., Strous, G.J., Crapo, J.D., Geuze, H.J., Slot, J.W. J. Cell Biol. (1993) [Pubmed]
  12. Distribution of newly synthesized lysosomal enzymes in the endocytic pathway of normal rat kidney cells. Ludwig, T., Griffiths, G., Hoflack, B. J. Cell Biol. (1991) [Pubmed]
  13. Increased cathepsin D-like activity in cortex, tubules, and glomeruli isolated from rats with experimental nephrotic syndrome. Baricos, W.H., Shah, S.V. Biochem. J. (1984) [Pubmed]
  14. Activities of cathepsin D in rat prostate during castration induced involution. Tanabe, E.T., Lee, C., Grayhack, J.T. J. Urol. (1982) [Pubmed]
  15. Potentiation of the protective effects of a converting enzyme inhibitor and a thromboxane synthetase inhibitor in hemorrhagic shock. Bitterman, H., Phillips, G.R., Dragon, G., Lefer, A.M. J. Pharmacol. Exp. Ther. (1987) [Pubmed]
  16. Immunohistochemical evidence for amyloid beta in rat soleus muscle in chloroquine-induced myopathy. Tsuzuki, K., Fukatsu, R., Takamaru, Y., Kimura, K., Abe, M., Shima, K., Fujii, N., Takahata, N. Neurosci. Lett. (1994) [Pubmed]
  17. Salutary consequences of blockade of platelet activating factor in hemorrhagic shock. Stahl, G.L., Bitterman, H., Terashita, Z., Lefer, A.M. Eur. J. Pharmacol. (1988) [Pubmed]
  18. Essential role for cathepsin D in bleomycin-induced apoptosis of alveolar epithelial cells. Li, X., Rayford, H., Shu, R., Zhuang, J., Uhal, B.D. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  19. Regulation of rat hepatocyte protein kinase C beta isoenzymes by the lipid peroxidation product 4-hydroxy-2,3-nonenal: A signaling pathway to modulate vesicular transport of glycoproteins. Chiarpotto, E., Domenicotti, C., Paola, D., Vitali, A., Nitti, M., Pronzato, M.A., Biasi, F., Cottalasso, D., Marinari, U.M., Dragonetti, A., Cesaro, P., Isidoro, C., Poli, G. Hepatology (1999) [Pubmed]
  20. The lysosomal protease cathepsin D is efficiently sorted to and secreted from regulated secretory compartments in the rat basophilic/mast cell line RBL. Dragonetti, A., Baldassarre, M., Castino, R., Démoz, M., Luini, A., Buccione, R., Isidoro, C. J. Cell. Sci. (2000) [Pubmed]
  21. Up-Regulation of Cation-Independent Mannose 6-Phosphate Receptor and Endosomal-Lysosomal Markers in Surviving Neurons after 192-IgG-Saporin Administrations into the Adult Rat Brain. Hawkes, C., Kabogo, D., Amritraj, A., Kar, S. Am. J. Pathol. (2006) [Pubmed]
  22. Cathepsin D released by lactating rat mammary epithelial cells is involved in prolactin cleavage under physiological conditions. Lkhider, M., Castino, R., Bouguyon, E., Isidoro, C., Ollivier-Bousquet, M. J. Cell. Sci. (2004) [Pubmed]
  23. Prolactin crinophagy is induced in the estrogen-stimulated male rat pituitary. Kuriakose, N.R., Reifel, C.W., Bendayan, M., Elce, J.S., Shin, S.H. Histochemistry (1989) [Pubmed]
  24. Isolation and sequencing of a cDNA clone encoding rat liver lysosomal cathepsin D and the structure of three forms of mature enzymes. Fujita, H., Tanaka, Y., Noguchi, Y., Kono, A., Himeno, M., Kato, K. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  25. Biochemical and immunohistochemical study on physiological activity and distribution of hepatic cathepsin D. Burdan, F., Szumilo, J., Korobowicz, A., Dudka, J., Korobowicz, E., Wallner, G., Maciejewski, R. Acta physiologica Hungarica. (2003) [Pubmed]
  26. Structures at the proteolytic processing region of cathepsin D. Yonezawa, S., Takahashi, T., Wang, X.J., Wong, R.N., Hartsuck, J.A., Tang, J. J. Biol. Chem. (1988) [Pubmed]
  27. Intracellular distribution of cathepsin D in rat corpora lutea in relation to reproductive state and the action of prostaglandin F2alpha and prolactin. Lahav, M., Meidan, R., Amsterdam, A., Gebauer, H., Lindner, H.R. J. Endocrinol. (1977) [Pubmed]
  28. Differential rat T cell recognition of cathepsin D-released fragments of mycobacterial 65 kDa heat-shock protein after immunization with either the recombinant protein or whole mycobacteria. van Noort, J.M., Anderton, S.M., Wagenaar, J.P., Wauben, M.H., van Holten, C., Boog, C.J. Int. Immunol. (1994) [Pubmed]
  29. Roles of cathepsins in reperfusion-induced apoptosis in cultured astrocytes. Takuma, K., Kiriu, M., Mori, K., Lee, E., Enomoto, R., Baba, A., Matsuda, T. Neurochem. Int. (2003) [Pubmed]
  30. Proteolytic enzymes in experimental spinal cord injury. Banik, N.L., Hogan, E.L., Powers, J.M., Smith, K.P. J. Neurol. Sci. (1986) [Pubmed]
  31. Preventive effect of naringin on cardiac markers, electrocardiographic patterns and lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats. Rajadurai, M., Stanely Mainzen Prince, P. Toxicology (2007) [Pubmed]
  32. Overexpression of a rat kinase-deficient phosphoinositide 3-kinase, Vps34p, inhibits cathepsin D maturation. Row, P.E., Reaves, B.J., Domin, J., Luzio, J.P., Davidson, H.W. Biochem. J. (2001) [Pubmed]
  33. Transient forebrain ischemia induces increased expression and specific localization of cathepsins E and D in rat hippocampus and neostriatum. Nakanishi, H., Tsukuba, T., Kondou, T., Tanaka, T., Yamamoto, K. Exp. Neurol. (1993) [Pubmed]
  34. Immunohistochemical characterization of the intracellular pool of water channel aquaporin-2 in the rat kidney. Tajika, Y., Matsuzaki, T., Suzuki, T., Aoki, T., Hagiwara, H., Tanaka, S., Kominami, E., Takata, K. Anatomical science international / Japanese Association of Anatomists. (2002) [Pubmed]
  35. Rat erythrocyte NADH-cytochrome b5 reductase. Quantitation and comparison between the membrane-bound and soluble forms using an antibody against the rat liver enzyme. Borgese, N., Macconi, D., Parola, L., Pietrini, G. J. Biol. Chem. (1982) [Pubmed]
  36. Detection of procathepsin D in rat milk. Benes, P., Koelsch, G., Dvorak, B., Fusek, M., Vetvicka, V. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. (2002) [Pubmed]
  37. Identification and characterization of a lysosomal transporter for small neutral amino acids. Sagné, C., Agulhon, C., Ravassard, P., Darmon, M., Hamon, M., El Mestikawy, S., Gasnier, B., Giros, B. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  38. Endosomal proteolysis of internalized insulin at the C-terminal region of the B chain by cathepsin D. Authier, F., Metioui, M., Fabrega, S., Kouach, M., Briand, G. J. Biol. Chem. (2002) [Pubmed]
  39. Regulation by insulin of amino acid release and protein turnover in the perfused rat hemicorpus. Jefferson, L.S., Li, J.B., Rannels, S.R. J. Biol. Chem. (1977) [Pubmed]
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