Abstract
Low density lipoproteins have been implicated in the pathogenesis of atherosclerosis. A study has therefore been made of their proteolytic degradation by homogenates of cultured smooth muscle cells from the pig aorta. The pH optimum of proteolysis of 125I-labelled low density lipoproteins was 4.25, thus suggesting the involvement of lysosomal cathepsins. Proteolysis at acid pH started to become saturated at low density lipoprotein concentrations of approx. 20 microgram of protein/ml, but did not obey Michaelis-Menten kinetics. After a lag period of approx. 10 min, proteolytic degradation was linear with time up to at least 4 h incubation, but showed a sigmoidal relationship with homogenate concentration. When cathepsin D was inhibited by pepstatin, the proteolysis of 125I-labeled low density lipoproteins was inhibited by more than 90%, whereas when cathepsin B was inhibited by leupeptin, the rate of proteolysis decreased by approx. 50%. Antipain, which inhibits both cathepsins A and B, did not inhibit proteolysis any more than leupeptin, thus suggesting a minor role, if any, for cathepsin A. a combination of pepstatin and either leupeptin or antipain inhibited proteolysis completely. Cathepsins B and D acted synergistically in ...Continue Reading
References
Apr 1, 1977·European Journal of Biochemistry·H KirschkeP Bohley
Feb 13, 1976·Biochimica Et Biophysica Acta·T NakaiT F Whayne
Mar 26, 1976·Biochimica Et Biophysica Acta·D B WeinsteinD Steinberg
Apr 1, 1976·Physiological Reviews·R L JacksonA M Gotto
Feb 23, 1977·Biochimica Et Biophysica Acta·Y SteinO Stein
Jan 1, 1977·Annual Review of Biochemistry·J L Goldstein, M S Brown
Nov 1, 1977·Circulation Research·H F HoffJ W Gaubatz
Jul 1, 1971·The Journal of Cell Biology·R Ross
Feb 21, 1972·Biochimica Et Biophysica Acta·D W BilheimerR I Levy
Apr 1, 1974·Experimental and Molecular Pathology·T J Peters, C De Duve
Jul 1, 1974·Circulation Research·E L BiermanY Stein
Nov 25, 1974·Biochimica Et Biophysica Acta·W HuismanM Gruber
Apr 1, 1972·The Biochemical Journal·A J Barrett, J T Dingle
Dec 1, 1972·The Journal of Antibiotics·H IkezawaH Umezawa
Jan 1, 1971·Annals of Internal Medicine·W B KannelP M McNamara
Jul 1, 1971·The Journal of Antibiotics·H IkezawaH Umezawa
Sep 1, 1955·The Journal of Clinical Investigation·R J HAVELJ H BRAGDON
Citations
Feb 1, 1983·Experimental and Molecular Pathology·D S LeakeT J Peters
Sep 6, 2002·The American Journal of Pathology·Sofia JormsjöPer Eriksson
Feb 28, 2006·Molecular Nutrition & Food Research·Dagmar FuchsUwe Wenzel
Feb 4, 2009·The FEBS Journal·Katrin KollmannTorben Lübke
Jun 15, 1989·European Journal of Biochemistry·M E Knowles, D S Leake
Mar 1, 1985·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·P S BachorikP O Kwiterovich
Mar 6, 2004·Circulation Research·Farouc A Jaffer, Ralph Weissleder
Aug 13, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Allan R BrasierMohsen S Eledrisi
Nov 7, 2018·Journal of Lipid Research·Feroz Ahmad, David S Leake
Jan 1, 1986·The Journal of Membrane Biology·U ScheuringD Schubert
Apr 22, 2018·Nature Reviews. Cardiology·Cong-Lin LiuGuo-Ping Shi
Nov 15, 1982·European Journal of Biochemistry·D S LeakeT J Peters
Feb 15, 1988·Klinische Wochenschrift·K Henze, G Wolfram
Nov 5, 1981·Biochimica Et Biophysica Acta·L de MarcoT J Peters
Sep 1, 1989·Atherosclerosis·S M RankinD S Leake
Jun 1, 1982·Atherosclerosis·H F Hoff, M G Bond
Sep 1, 1982·Atherosclerosis·D S Leake, T J Peters