Biology subjects

El Sayed, A.

Publications and source records attributed to El Sayed, A..

4 recordsLinked to original sources

bioRxiv2025

Lysosomal accumulation of Masitinib alters autophagy via pH-dependent trapping.

Masitinib is an oral tyrosine kinase inhibitor developed initially for the treatment of mastocytosis. Preclinical studies suggest that masitinib can modulate mast cell activity and neuroinflammation, making it a potential therapeutic candidate for neurodegenerative diseases. However, clinical outcomes remain inconclusive, which may be linked to a lack of understanding of its molecular mechanism of action and potential off-target effects. Using a panel of cancer cell lines, we found that masitinib suppresses mTORC1 activity while simultaneously inducing AKT phosphorylation. Interestingly, thermal proteome profiling analysis revealed that lysosomal proteins were the most thermally affected by masitinib. Using large unilamellar vesicle systems that mimic the lipid composition and physicochemical environment of lysosomal membranes, we observed that masitinib preferentially accumulates in acidic vesicle membranes, consistent with a pH-dependent trapping mechanism. Furthermore, cellular assays demonstrated that masitinib disrupts autophagy by impairing lysosomal acidification. Together, these findings elucidate the lysosomal accumulation of masitinib, providing a molecular basis for its mechanism of action.

pharmacology and toxicology↗

bioRxiv2025

Mechanistic Insights into TYSM Protein Regulation by mTORC2 in Response to Chemotherapy.

Transcriptional and translation control of thymidylate synthase (TYMS) is poorly understood, particularly in response to chemotherapeutic drugs such as 5-Fluorouracil (5-FU) and its derivatives. The current study addressed this gap by demonstrating a biphasic response in TYMS protein levels upon 5-FU treatment. Indeed, we observe an initial reduction within the first few hours, followed by a marked increase at 24 hours. These changes occurred independently of transcriptional regulation, as TYMS mRNA levels remained stable during the early phase and showed only a moderate increase later. We further showed that neither autophagy nor proteasomal degradation contributed to this dynamic, but instead it is driven by change in its translation. Using thermal proteome profiling, we identified SIN1, a key component of the mTORC2 complex, as a key regulator of TYMS protein levels. Functional studies revealed that SIN1 depletion negatively alters TYMS levels and dynamics and sensitizes cancer cells to 5-FU-mediated cell death. These findings uncover a novel mechanism controlling TYMS protein levels and suggest that targeting SIN1 may represent a promising strategy to enhance the therapeutic efficacy of 5-FU-based treatments.

biochemistry↗

bioRxiv2016

Development of 2-phenylethanol plus acetic acid lures to monitor obliquebanded leafroller (Lepidoptera: Tortricidae) under mating disruption

We evaluated the effectiveness of 2-phenylethanol (PET) in combination with acetic acid (AA) as a binary lure for monitoring male and female obliquebanded leafroller, Choristoneura rosaceana (Harris). Studies were conducted in apple, Malus domestica Borkhausen, orchards treated with or without sex pheromone dispensers for mating disruption (MD). Open polypropylene vials, closed membrane cups, and rubber septa loaded with AA and/or PET in varying amounts were first evaluated in a series of trapping experiments. Membrane cups loaded with 800 mg of PET were as effective as 10-mg septa, but longer lasting, and were comparable to the open vials. A membrane cup AA lure was effective in tests, but further work is needed to increase its release rate and extend its activity. Catches of codling moth, Cydia pomonella (L.), and C. rosaceana were unaffected by combining PET with (E,E)-8,10-dodecadien-1-ol, the sex pheromone of codling moth, pear ester, (E,Z)-2,4-ethyl-decadienoate, and AA lures. Adding (E)-4,8-dimethyl-1,3,7-nonatriene to this blend to enhance codling moth catch, significantly reduced catches of C. rosaceana. PET+AA was a more attractive binary lure than AA plus phenylacetonitrile (PAN) for C. rosaceana. The addition of PET or PAN to traps already baited with the sex pheromone of C. rosaceana significantly reduced male catches. Traps baited with PET+AA placed in blocks not treated with MD caught significantly fewer C. rosaceana than traps baited with sex pheromone. In comparison, sex pheromone-baited traps in MD blocks caught [≤] 1 male moth per season which was significantly lower than total moth (> 10) or female moth ([≥] 3) catch in these blocks with PET+AA. A high proportion (> 70%) of trapped females were mated in both untreated and MD-treated orchards. Further refinement of this binary, bisexual lure using membrane cup technology may allow the establishment of action thresholds and improve management timings for C. rosaceana.

ecology↗

bioRxiv2016

First record of double-edged sword effect of caterpillar-induced plant volatiles in nature

Plants release volatiles in response to caterpillar feeding that attract natural enemies of the herbivores, a tri-trophic interaction which has been considered an indirect plant defence against herbivores. The caterpillar-induced plant volatiles have been reported to repel or attract conspecific adult herbivores. Apple seedlings infested with Pandemis pyrusana larvae uniquely release five compounds (benzyl alcohol, benzyl nitrile, phenylacetaldehyde, indole, and (E)-nerolidol). These compounds and other known caterpillar-induced plant volatiles were tested to investigate the response of both herbivores and natural enemies. In field tests, binary blends of benzyl nitrile and acetic acid or 2-phenylethanol and acetic acid attracted a large number of conspecific male and female adult moths. On the other hand, a ternary blend of benzyl nitrile, 2-phenylethanol and acetic acid attracted the largest numbers of the general predator, the common green lacewing, Chrysoperla carnea. This study provides the first record of caterpillar-induced plant volatile attraction to conspecific adult herbivores as well as predators under natural conditions.

ecology↗