On the mechanism of inhibition of NADH oxidase by ubiquinone-3

The combined effects of rotenone and ubiquinone-3 on the kinetics of NADH dehydrogenase and NADH oxidase have been investigated. The two inhibitors do not show additivity; on the other hand, ubiquinone-3, when preincubated with the enzyme, partially removes rotenone sensitivity. The inhibition of NADH oxidase by ubiquinone-3 is the result of at least two combined effects: the competition of the less active ubiquinone-3 with endogenous ubiquinone-10 in the acceptor site of the dehydrogenase, and a nonspecific action on the structure of complex I. The latter effect is perhaps mediated by a physical change of the phospholipid bilayer similar to that observed with agents such as butanol, perturbing lipid-protein interactions in the membrane.     

Chromosome 11p15 deletions in human malignant astrocytomas and primitive neuroectodermal tumors.

Chromosome 11p15 deletions occur frequently in several types of human cancer, both sporadic and familial, suggesting that a tumor suppressor gene is present within the deleted chromosome region. We carried out a restriction fragment length polymorphism analysis of chromosome 11p in two types of human brain tumors: malignant astrocytoma, the most common glial tumor in adults; and primitive neuroectodermal tumor (PNET), a malignant embryonic tumor that afflicts children. Loss of heterozygosity was found in 11/43 malignant astrocytomas (26%) and in 3/11 PNETs (27%). Deletion mapping revealed a region of loss on chromosome 11p (p15.4-pter) that was common to both tumor types. To determine whether the c-H-ras gene, located on chromosome 11p in the common region of deletion, was a candidate gene, we analyzed polymerase chain reaction products corresponding to all four c-H-ras coding exons for single-strand conformation polymorphisms. The absence of electrophoretic mobility shifts in tumor DNA compared to leukocyte DNA indicated that c-H-ras gene mutations were most likely not present. These results suggested that loss of a gene on chromosome 11p15 distinct from c-H-ras is an important step in tumorigenesis within the central nervous system in both children and adults.