Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracisternal granules (ICG) develop in the rough ER of hyperstimulated thyrotrophs or thyroid hormone-secreting cells of the anterior pituitary gland. To determine the fate of these granules, we carried out morphological and immunocytochemical studies on pituitaries of thyroxine-treated, thyroidectomized rats. Under these conditions the ER of thyrotrophs is dramatically dilated and contains abundant ICG; the latter contain beta subunits of thyrotrophic hormone (TSH-beta). Based on purely morphologic criteria, intermediates were identified that appeared to represent stages in the transformation of a part rough/part smooth ER cisterna into a lysosome. Using immunocytochemical and cytochemical markers, two major types of intermediates were distinguished: type 1 lacked ribosomes but were labeled with antibodies against both ER markers (PDI, KDEL, ER membrane proteins) and a lysosomal membrane marker, lgp120. They also were reactive for the lysosomal enzyme, acid phosphatase, by enzyme cytochemistry. Type 2 intermediates were weakly reactive for ER markers and contained both lgp120 and lysosomal enzymes (cathepsin D, acid phosphatase). Taken together these results suggest that in hyperstimulated thyrotrophs part rough/part smooth ER elements containing ICG lose their ribosomes, their membrane is modified, and they sequentially acquire a lysosome-type membrane and lysosomal enzymes. The findings are compatible with the conclusion that a pathway exists by which under certain conditions, secretory proteins present in the ER as well as ER membrane and content proteins can be degraded by direct conversion of ER cisternae into lysosomes.
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PMID:A non-autophagic pathway for diversion of ER secretory proteins to lysosomes. 152 75

In experiments on albino male rats the dependence of the cathepsin D activity on the thyroid hormone- and somatotropin levels in the organism was studied. It was demonstrated that the total cathepsin D activity in the liver of hypothyroid rats is lowered by 37% and that of hyperthyroid animals is augmented by 63%. Somatotropin injected to intact rats within 10 days in doses of 0.5 mg/100 g body weight enhanced the total enzyme activity by 19%. Hormone injection to hypothyroid animals returns to the normal cathepsin D activity, whereas in hyperthyroid rats the enzyme effect is significantly lowered under hormone action. Protein content in the nucleus-free homogenate of the hypothyroid rat liver does not differ from that of intact rats and is increased by 27% in hyperthyroid animals. Exogenous somatotropin returns to normal protein content in hyperthyroid rats.
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PMID:[Effect of somatotropin on cathepsin D in the liver of hypo- and hyperthyroid rats]. 673 55

Cathepsin D, an aspartyl protease, plays a key role in the metabolic degradation of intracellular proteins in an acidic milieu of lysosomes. Proteolysis plays an essential role in anuran tail regression and a wide variety of thyroid hormone induced proteolytic enzymes have been reported to be involved in the regressing tail. The present study describes the trend of specific activity of cathepsin D in the tail of different developmental stages and immunohistochemical localization of cathepsin D during degradation of various tail tissues in the tadpoles of Polypedates maculatus. Cathepsin D has been found to be involved in the degradation of major tail tissues such as epidermis, muscle, spinal cord, notochord cells and blood cells in the regressing tail. Interestingly, it has also been found to be involved in the pre-regressing tail prior to visible tail regression. In addition, melanocytes have been described to be associated with degradation of different tail tissues.
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PMID:Involvement of cathepsin D during tail regression in tadpoles of the common Indian tree frog, Polypedates maculatus (Anura: Rhacophoridae). 2119 62

Resistance of cancer cells to chemotherapeutic agents is one of the main causes of treatment failure. In order to detect proteins potentially involved in the mechanism of resistance to taxanes, we assessed differences in protein expression in MCF-7 breast cancer cells that are sensitive to paclitaxel and in the same cells with acquired resistance to paclitaxel (established in our lab). Proteins were separated using two-dimensional electrophoresis. Changes in their expression were determined and proteins with altered expression were identified using mass spectrometry. Changes in their expression were confirmed using western blot analysis. With these techniques, we found three proteins expressed differently in resistant MCF-7 cells, i.e., thyroid hormone-interacting protein 6 (TRIP6; upregulated to 650%), heat shock protein 27 (HSP27; downregulated to 50%) and cathepsin D (downregulated to 28%). Silencing of TRIP6 expression by specific siRNA leads to decreased number of grown resistant MCF-7 cells. In the present study we have pointed at some new directions in the studies of the mechanism of resistance to paclitaxel in breast cancer cells.
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PMID:Differentially expressed proteins in human MCF-7 breast cancer cells sensitive and resistant to paclitaxel. 2555 73