Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a first step in studies on the molecular mechanism(s) underlying gentamicin toxicity, the effect of treating rats with this aminoglycoside antibiotic (100 mg/kg once or twice daily for 3 days) on the analytical subfractionation of the kidney cortex has been examined. DNA was used as a marker for the nuclei, cytochrome oxidase for mitochondria, acid phosphatase for lysosomes, catalase for peroxisomes (with reservations; see the companion paper), NADPH-cytochrome c reductase for the endoplasmic reticulum, p-nitrophenyl-alpha-mannosidase (at pH 5.5) for the Golgi apparatus, AMPase for the plasma membrane in general and alkaline phosphatase for the brush border, and lactate dehydrogenase for the cytosol. In addition, the presumptive lysosomal hydrolases N-acetyl-beta-D-glucosaminidase, p-nitrophenyl-alpha-mannosidase (at pH 4.5), cathepsin D, and DNase II were monitored. Electron microscopy was also performed on the subfractions obtained. The only significant biochemical changes brought about by gentamicin treatment were that N-acetyl-beta-D-glucosaminidase demonstrated both a greater total activity and a larger enrichment in the 104,000gav pellet, while p-nitrophenyl-alpha-mannosidase at pH 4.5 demonstrated the same total activity and a greater enrichment in the 104,000gav pellet. Since myeloid bodies were shown by electron microscopy to sediment primarily with the 500gav and 10,000gav pellets, the biochemical changes seen cannot be associated with these morphological structures. These findings suggest that selective changes in a certain subpopulation(s) of lysosomes or in certain lysosomal enzymes may be involved in the early stages of gentamicin toxicity. On the other hand, no lysosomal membrane damage was observed here, since both the latency of acid phosphatase and the recovery of this activity in the soluble cytosol were unchanged. The present investigation may also have relevance for the dosage and duration of gentamicin treatment chosen in clinical situations.
 ...
PMID:Biochemical effects of gentamicin on rat kidney cortex. II. Analytical subfractionation after short-term, high-dose treatment. 303 Aug

A strain derived from a colony of BALB/c mice at the National Center for Toxicological Research, Jefferson, AR, USA (NCTR-BALB/c) suffers from an autosomal recessive disorder characterized by proliferation of secondary lysosomes with accumulation ofunesterified cholesterol in several tissues. The unesterified cholesterol content of spleens and lungs from the affected mice were elevated 8- and 3-fold respectively over age- and sex-matched controls. Postnuclear supernatants of tissue homogenates were fractionated by sucrose density gradient centrifugation and the fractions were analyzed for unesterified cholesterol, protein and marker enzyme activities for lysosomes (N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase), plasma membrane (alkaline phosphodiesterase I), endoplasmic reticulum (glucose-6-phosphatase) and mitochondria (cytochrome oxidase). The enzyme distribution profile showed that lysosomes of affected tissues floated at low density regions (density 1.05-1.08) of the gradient and contained substantial amount of tissue unesterified cholesterol. These low density lysosomes were purified about 17-fold (58% yield) from spleen and about 6-fold (32% yield) from lungs with minimal contamination by other organelles They were mostly intact as judged by high latency for N-acetyl-beta-D-glucosaminidase activity (70-100%). Lysosomes of control tissues were not found at the low density regions. The distribution profiles for other organelles were similar between affected and control tissues. Phospholipid composition of low density lysosomes were distinctly different from their respective tissue homogenates. Spleen and lung lysosomes were enriched in sphingomyelin and phosphatidylcholine respectively. The results suggest that these lysosomes acquire their low densities due to accumulation of unesterified cholesterol, the retention of which may be aided by sphingomyelin and phosphatidylcholine content of the lysosomes.
 ...
PMID:Lysosome lipid storage disorder in NCTR-BALB/c mice: spleen and lung lysosomes store unesterified cholesterol but differ in their phospholipid composition. 1119 85