40 research outputs found
Impact of Cytochrome P450 Enzymes on the Phase I Metabolism of Drugs
The cytochrome P450 (CYP) enzyme family is the major enzyme system catalyzing the phase
I metabolism of xenobiotics, including pharmaceuticals and toxic compounds in the environment.
A major part of the CYP-dependent xenobiotic metabolism is due to polymorphic and inducible
enzymes, which may, quantitatively or qualitatively, alter or enhance drug metabolism and toxicity.
Drugâdrug interactions are major mechanisms caused by the inhibition and/or induction of CYP
enzymes. Particularly, CYP monooxygenases catalyze hydroxylation reactions to form hydroxylated
metabolites. The secondary metabolites are sometimes as active as the parent compound, or even
more active. The aim of this review is to summarize some of the significative examples of common
drugs used for the treatment of diverse diseases and underline the activity and/or toxicity of
their metabolites
Thidiazuron: New Trends and Future Perspectives to Fight Xylella fastidiosa in Olive Trees
These days, most of our attention has been focused on the COVIDâ19 pandemic, and we
have often neglected what is happening in the environment. For instance, the bacterium Xylella fasâ
tidiosa reâemerged as a plant pathogen of global importance in 2013 when it was first associated
with an olive tree disease epidemic in Italy, called Olive Quick Decline Syndrome (OQDS), specifiâ
cally caused by X. fastidiosa subspecies pauca ST53, which affects the Salento olive trees (Apulia,
SouthâEast Italy). This bacterium, transmitted by the insect Philaenus spumarius, is negatively reâ
shaping the Salento landscape and has had a very high impact in the production of olives, leading
to an increase of olive oil prices, thus new studies to curb this bacterium are urgently needed. Thidiâ
azuron (TDZ), a diphenylurea (Nâphenylâ1,2,3âthiadiazolâ5âyl urea), has gained considerable attenâ
tion in recent decades due to its efficient role in plant cell and tissue culture, being the most suitable
growth regulator for rapid and effective plant production in vitro. Its biological activity against
bacteria, fungi and biofilms has also been described, and the use of this lowâcost compound to fight
OQDS may be an intriguing ide
Microtubules play a role in trafficking prevacuolar compartments to vacuoles in tobacco pollen tubes
Fine regulation of exocytosis and endocytosis plays a basic role in pollen tube growth.
Excess plasma membrane secreted during pollen tube elongation is known to be retrieved by endocytosis and partially reused in secretory pathways through the Golgi apparatus. Dissection of
endocytosis has enabled distinct degradation pathways to be identified in tobacco pollen tubes and has shown that microtubules influence the transport of plasma membrane internalized in the tip region to vacuoles. Here we used different drugs affecting the polymerization state of microtubules together with SYP21, a marker of prevacuolar compartments, to characterize trafficking of prevacuolar compartments in Nicotiana tabacum pollen tube. Ultrastructural and biochemical analysis showed that microtubules bind SYP21-positive microsomes. Transient transformation of pollen tubes with LAT52-YFP-SYP21 revealed that microtubules play a key role in the delivery of prevacuolar compartments to tubular vacuoles
Coupling to a cancer-selective heparan-sulfate-targeted branched peptide can by-pass breast cancer cell resistance to methotrexate
Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines. We found that MTX-conjugated NT4 allows drug resistance to be by-passed in MTX-resistant human breast cancer cells lacking expression of folate reduced carrier. NT4 peptides appear to be extremely promising cancer-selective targeting agents that can be exploited as theranostics in personalized oncological applications
Protein Analysis of Pollen Tubes after the Treatments of Membrane Trafficking Inhibitors Gains Insights on Molecular Mechanism Underlying Pollen Tube Polar Growth
Pollen tube elongation is characterized by a highly-polarized tip growth process dependent on an efficient vesicular transport system and largely mobilized by actin cytoskeleton. Pollen tubes are an ideal model system to study exocytosis, endocytosis, membrane recycling, and signaling network coordinating cellular processes, structural organization and vesicular trafficking activities required for tip growth. Proteomic analysis was applied to identify Nicotiana tabacum Differentially Abundant Proteins (DAPs) after in vitro pollen tube treatment with membrane trafficking inhibitors Brefeldin A, Ikarugamycin and Wortmannin. Among roughly 360 proteins separated in two-dimensional gel electrophoresis, a total of 40 spots visibly changing between treated and control samples were identified by MALDI-TOF MS and LCâESIâMS/MS analysis. The identified proteins were classified according to biological processes, and most proteins were related to pollen tube energy metabolism, including ammino acid synthesis and lipid metabolism, structural features of pollen tube growth as well modification and actin cytoskeleton organization, stress response, and protein degradation. In-depth analysis of proteins corresponding to energy-related pathways revealed the male gametophyte to be a reliable model of energy reservoir and dynamics