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Biomedical subjects

D R Sherman

Publications and source records attributed to D R Sherman.

8 recordsLinked to original sources
PubMed1992

Components of sterol biosynthesis assembled on the oxygen-avid hemoglobin of Ascaris.

The parasitic nematode Ascaris infests a billion people worldwide. Much of its proliferative success is due to prodigious egg production, up to 10(6) sterol-replete eggs per day. Sterol synthesis requires molecular oxygen for squalene epoxidation, yet oxygen is scarce in the intestinal folds the worms inhabit. Ascaris has an oxygen-avid hemoglobin in the perienteric fluid that bathes its reproductive organs. Purified hemoglobin contained tightly bound squalene and functioned as an NADPH-dependent, ferrihemoprotein reductase. All components of the squalene epoxidation reaction--squalene, oxygen, NADPH, and NADPH-dependent reductase--are assembled on the hemoglobin. This molecule may thus function in sterol biosynthesis.

Animals↗
PubMed1992

Ascaris hemoglobin gene: plant-like structure reflects the ancestral globin gene.

Animal globin genes have two introns at strictly conserved positions, while plant globin genes have both of these as well as an additional, central intron. It has been proposed that a common ancestor gene had three introns, one of which was subsequently lost from animal but not plant globin genes. We have elucidated the cDNA sequence and gene structure of a hemoglobin from the parasitic nematode Ascaris suum and found a plant-like central intron, providing strong evidence for a three-intron ancestor of modern globin genes.

Amino Acid Sequence↗
PubMed1991

Anatomy of the parp gene promoter of Trypanosoma brucei.

While growing in the tsetse fly, Trypanosoma brucei expresses a major surface glycoprotein, the procyclic acidic repetitive protein (PARP). The parp genes are transcribed by an alpha-amanitin-resistant RNA polymerase. We have determined the sequence requirements for parp promoter activity. Studies of RNA produced from input DNA in transiently transfected trypanosomes indicate that the RNA is correctly processed by trans-splicing and polyadenylation. Deletion analyses show that 330 bp are sufficient for full promoter and splicing activity and that the promoter structure is complex, involving at least three elements whose mutual spacing is important. Mutagenesis pin-pointed two sequences vital for promoter activity; neither bears any resemblance to known prokaryotic or eukaryotic promoter elements.

Animals↗
PubMed1990

Transcription of the procyclic acidic repetitive protein genes of Trypanosoma brucei.

The procyclic acidic repetitive protein (parp) genes of Trypanosoma brucei encode a small family of abundant surface proteins whose expression is restricted to the procyclic form of the parasite. They are found at two unlinked loci, parpA and parpB; transcription of both loci is developmentally regulated. The region of homology upstream of the A and B parp genes is only 640 base pairs long and may contain sequences responsible for transcriptional initiation and regulation. Transcription upstream of this putative promoter region is not developmentally regulated and is much less active than that of the parp genes; the polymerase responsible is inhibited by alpha-amanitin, whereas that transcribing the parp genes is not. Transcription of the parp genes is strongly stimulated by low levels of UV irradiation. The putative parp promoter, when placed upstream of the chloramphenicol acetyltransferase gene, is sufficient to cause production of chloramphenicol acetyltransferase in a T. brucei DNA transformation assay. Taken together, these results suggest that a promoter for an alpha-amanitin-resistant RNA polymerase lies less than 600 nucleotides upstream of the parp genes.

Animals↗
PubMed1987

Rat cellular retinol-binding protein: cDNA sequence and rapid retinol-dependent accumulation of mRNA.

Cellular retinol-binding protein (CRBP) may be an important mediator of vitamin A action. We report here the identification of a cDNA clone corresponding to the rat CRBP gene. The cDNA is 695 nucleotides long, with an open reading frame corresponding to a protein of 134 amino acids. The deduced amino acid sequence is identical with that of rat CRBP. The nucleotide sequence shows 90.5% similarity with the human CRBP cDNA sequence. Genomic DNA analysis indicates that CRBP is present in one, or at most two, copies within the rat genome. Analysis of mRNA reveals a single species in every tissue tested and suggests that the isolated cDNA is full-length. Finally, when retinol-deficient rats are fed retinyl acetate for 4 hr, about 4-fold accumulation of CRBP-specific mRNA is observed in the lungs. This rapid effect suggests that the micronutrient retinol may directly influence the expression of its specific intracellular binding protein.

Amino Acid Sequence↗
PubMed1987

How do retinoids work?

The main physiological function of natural retinoids, i.e. the dietary micronutrient retinol and its metabolite retinoic acid, is in proper differentiation and maintenance of differentiated state of many if not all epithelia. Also, it appears that the metabolism of nonepithelial cells can be affected by these compounds. The effects are diverse. Although the exact molecular mechanism causing these effects remain to be elucidated, recent research indicates that both retinol and retinoic acid affect genomic expression by activating and simultaneously repressing specific genes. Such action results in the appearance and disappearance of more than 40 specific proteins. The effect on the genomic expression is time-dependent. Some of the genes are influenced very soon in a matter of a few hours. Effects on other genes require considerable time. Whether natural retinoids interact with the genome directly remains to be shown. How such interactions could occur is discussed.

Carrier Proteins↗