Effects of various basic compounds on the degradation of formaldehyde-treated 125I-labeled bovine serum albumin in mouse liver lysosomes.
The effect of various basic compounds on degradation of formaldehyde-treated 125I-bovine serum albumin (denatured 125I-BSA) in livers of mice was studied in detail. Five basic compounds (BTTB, chloroquine, methylamine, ammonium chloride, and vinblastine) were tested. All the basic compounds inhibited the degradation of exogenous protein in lysosomes. When p-biphenylmethyl-(dl-tropyl-alpha-tropinium)bromide (BTTB) was used, the most effective inhibition was obtained at the concentration of 3.2 mM. Also, vinblastine, a well-known inhibitor of microtubular function, inhibited the degradation of an exogenous protein to the similar extent as that of chloroquine. The inhibition of protein degradation caused by BTTB closely related to the uptake of BTTB into lysosomes. It is supposed that BTTB accumulates in lysosomes and that it inhibits the hydrolytic enzyme by neutralizing intralysosomal pH. Furthermore, it is supposed that BTTB, a quaternary ammonium compound, becomes a useful tool in the study of protein degradation in lysosomes as well as the typically lysosomotropic compounds (chloroquine, ammonium chloride, and methylamine).
D000135:Acid Phosphatase / Q000378:metabolism; D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D011489:Protein Denaturation; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000378:metabolism*; D013997:Time Factors; D014747:Vinblastine / Q000494:pharmacology*
D000643:Ammonium Chloride; D005557:Formaldehyde; D012710:Serum Albumin, Bovine; D014747:Vinblastine; D002738:Chloroquine; D000135:Acid Phosphatase