11 research outputs found
Over-the-Counter Monocyclic Non-Steroidal Anti-Inflammatory Drugs in Environment—Sources, Risks, Biodegradation
Recently, the increased use of monocyclic
non-steroidal anti-inflammatory drugs has resulted in
their presence in the environment. This may have
potential negative effects on living organisms. The
biotransformation mechanisms of monocyclic nonsteroidal
anti-inflammatory drugs in the human body
and in other mammals occur by hydroxylation and
conjugation with glycine or glucuronic acid.
Biotransformation/biodegradation of monocyclic
non-steroidal anti-inflammatory drugs in the environment
may be caused by fungal or bacterial microorganisms.
Salicylic acid derivatives are degraded by
catechol or gentisate as intermediates which are
cleaved by dioxygenases. The key intermediate of
the paracetamol degradation pathways is hydroquinone.
Sometimes, after hydrolysis of this drug, 4-
aminophenol is formed, which is a dead-end metabolite.
Ibuprofen is metabolized by hydroxylation or
activation with CoA, resulting in the formation of
isobutylocatechol. The aim of this work is to attempt
to summarize the knowledge about environmental risk
connected with the presence of over-the-counter antiinflammatory
drugs, their sources and the biotransformation
and/or biodegradation pathways of these
drugs
Specialized Yeast Ribosomes: A Customized Tool for Selective mRNA Translation
Evidence is now accumulating that sub-populations of ribosomes - so-called specialized ribosomes - can favour the translation of subsets of mRNAs. Here we use a large collection of diploid yeast strains, each deficient in one or other copy of the set of ribosomal protein (RP) genes, to generate eukaryotic cells carrying distinct populations of altered ‘specialized’ ribosomes. We show by comparative protein synthesis assays that different heterologous mRNA reporters based on luciferase are preferentially translated by distinct populations of specialized ribosomes. These mRNAs include reporters carrying premature termination codons (PTC) thus allowing us to identify specialized ribosomes that alter the efficiency of translation termination leading to enhanced synthesis of the wild-type protein. This finding suggests that these strains can be used to identify novel therapeutic targets in the ribosome. To explore this further we examined the translation of the mRNA encoding the extracellular matrix protein laminin ?3 (LAMB3) since a LAMB3-PTC mutant is implicated in the blistering skin disease Epidermolysis bullosa (EB). This screen identified specialized ribosomes with reduced levels of RP L35B as showing enhanced synthesis of full-length LAMB3 in cells expressing the LAMB3-PTC mutant. Importantly, the RP L35B sub-population of specialized ribosomes leave both translation of a reporter luciferase carrying a different PTC and bulk mRNA translation largely unaltered