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)

In aqueous solution bovine myelin basic protein has a close-to-random coil structure that is partially transformed to helix on interaction with lipids. Circular dichroism spectra have been used to follow this conformational transition which, with phospholipids, decreases in the order phosphatidylglycerol, phosphatidic acid approximately equal to phospholipids, decreases in the order phosphatidylethanolamine. There appears to be a strong correlation between the extent of alpha-helix formation and the degree of penetration of the hydrophobic region of the bilayer, as assessed by other methods. Cholesterol mixed in bilayers with phosphatidylserine has little effect on the protein secondary structure. Although basic protein binds strongly to cerebroside and to cerebroside sulphate, two of the other major myelin lipids, the intrinsic chirality of these lipids precludes assessment of their effect on the protein conformation. No significant changes in the circular dichroism spectra accompany the protein association with either of the zwitterionic bilayer-forming lipids, phosphatidylethanolamine and phosphatidylcholine. This seems to exclude extensive penetration into bilayers of these lipids and hence to exclude appreciable hydrophobic interactions; on the other hand, it is argued that little evidence exists for ionic attractions to these lipids. The optical activity of peptides derived from the basic protein by cleavage at the 42-43 and 88-89 peptides bonds (with cathepsin D) and at the 115-116 bond (with a skatole derivative) has also been measured in an attempt to locate the helix-forming regions within the primary structure.
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PMID:Dependence on lipid structure of the coil-to-helix transition of bovine myelin basic protein. 616 92

We have previously shown that oxidized low-density lipoprotein (LDL) induces damage to the macrophage lysosomal membranes, with ensuing leakage of lysosomal contents and macrophage cell death. Cholesterol oxidation products (ChOx) have been reported to be the major cytotoxic components of oxidized LDL/LDL- and also to stimulate cholesterol accumulation in vascular cells. In the present study, we characterized the initial events during macrophage damage induced by cholesterol oxidation products (ChOx). Within 24 h of exposure, ChOx caused lysosomal destabilization, release to the cytosol of the lysosomal marker-enzyme cathepsin D, apoptosis, and postapoptotic necrosis. Enhanced autophagocytosis and chromatin margination was found 12 h after the exposure to ChOx, whereas apoptosis and postapoptotic necrosis was pronounced 24 and 48 h after the exposure. Some lysosomal vacuoles were then filled with degraded cellular organelles, indicating phagocytosis of apoptotic bodies by surviving cells. Because caspase-3 activation was detected in the ChOx-exposed cells, lysosomal destabilization may associate with the leakage of lysosomal enzymes, and activation of the caspase cascade. MnSOD mRNA levels were markedly increased after 24 h of exposure to ChOx, suggesting associated induction of mitochondrial protection repair or turnover. We conclude that ChOx-induced damage to lysosomes and mitochondria are sequelae to the cascade of oxysterol cytotoxic events. The early disruption of lysosomes induced by ChOx, with resultant autophagocytosis may be a critical event in apoptosis and/or necrosis of macrophages/foam cells during the development of atherosclerotic lesions.
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PMID:Lysosomal destabilization during macrophage damage induced by cholesterol oxidation products. 1128 Dec 88