Biology subjects

Gargouri, A.

Publications and source records attributed to Gargouri, A..

4 recordsLinked to original sources

bioRxiv2025

Biological evaluation and molecular docking study of Ferrociphenol as an anti-melanogenic agent

Cutaneous hyperpigmentation disorders are associated with abnormal accumulation of melanin pigments, which can be treated using depigmenting agents. In the present study, we investigated the effect of ferrociphenol (Fc-diOH), an organometallic intermediate used for the synthesis of hydroxy-ferrocifen derivatives, which has previously been shown as an inhibitor of Sepia tyrosinase activity, on the inhibition of melanogenesis in B16F10 melanoma cells. Cell viability, melanin quantification and tyrosinase activity assay demonstrated that Fc-diOH treatment reduced the amount of intracellular melanin and tyrosinase activity by 32 and by 25%, respectively, in B16F10 melanoma cells at 25 nM without significant cellular toxicity. Furthermore, the biological activity of Fc-diOH against melanogenesis was confirmed in in vivo experiments using zebrafish Danio rerio embryos. We found that Fc-diOH inhibited melanin production and tyrosinase activity of zebrafish embryos treated with 0.5 and 2 {micro}M respectively, without affecting embryonic development or viability. In addition and interestingly, molecular docking analysis demonstrates that the p-hydroxyphenyl groups of Fc-diOH make close contacts with the active site of tyrosinase, compared to arbutin and phenylthiourea, which could be due to its structural homology with the tyrosinase substrate. Therefore, these results strongly suggest that Fc-diOH decreases tyrosinase activity, thereby negatively regulating melanogenesis in B16F10 cells and zebrafish embryos. Thus, Fc-diOH could be used as a depigmentation agent for the treatment of various hyper-pigmentation disorders.

cell biology↗

bioRxiv2025

Intriguing relationship between chromosome I nuclear aneuploidy and mitochondrial intron deletion in yeast

A curious phenomenon was discovered when examining revertant colonies of the M3041 mutant located in the second intron of mitochondrial cytochrome b gene of Sacchromyces cerevisiae. Several colonies carrying a sector appeared on selective glycerol medium and all correspond to a reversion of M3041 by intron deletion. Colonies of revertants resulting from classical reversion were never sectored. The cells of the sectors, called S, presented a very typical growth profile on glycerol (selective medium for respiration) which differs from that of the rest of the colony called AS for anti-sector. The profiles are identical on glucose-based medium. Molecular analysis, by Pulsed Field Gel Electophoresis, of the S cells showed that they had lost one copy of chromosome 1, suggesting that the original a-haploid mutant had diploidized into mat (a/a). The aneuploid state was validated by crossing with a genetically marked strain followed by mass spore analysis. We then asked whether the aneuploid genetic background would influence the frequency of reversion by intron deletion. This was achieved through the conversion of S and AS cells to rho0 followed by cytoduction of mitochondria carrying M3041 or W91 mutations, knowing that W91 never reverses by intron deletion. Interestingly, there are significantly more revertants (by intron deletion) in the S than AS context for M3041, whereas W91 reversed with the same frequency in both contexts. Nuclear aneuploidy therefore promotes mitochondrial reversion by intron-deletion. We conclude that there is a particular relationship between nuclear aneuploidy and intron deletion during the reversion of mitochondrial intron mutations in yeast.

genetics↗

bioRxiv2024

Evidences of an inhibitory effect and other functions of human P53 in Escherichia coli

The human tumor suppressor P53 has so far been shown to inhibit growth in the yeast model as well as in other eukaryotic contexts. Despite a considerable number of sudies involving p53 in bacteria, the question of effects on cell growth and viability has never been explored. In this work, we report similar negative effect on cell viability of the protein expressed in Escherichia coli strain BL21(DE3). This inhibition still needs to be characterized in lights of the distinction between yeast and other organisms with different P53-caused deaths and pathways. Primary tests leaned towards an active p53 in this bacterial context, both under normal and stresseful conditions. Special effects were noticed either with phage infection or antibiotic treatment, using a GST-p53 fusion form. These results open the way for further investigations involving P53 in prokaryote systems.

cell biology↗

bioRxiv2023

Phage libraries screening on P53: yield improvement by zinc and a new parasites integrating analysis and rationale

P53 is a transcription factor that controls a variety of genes, primarily involved in cell cycle and other processes related to cell survival and death. We have isolated peptides targeting P53 (protein and domains) using the "phage display" technique. Interestingly, adding ZnCl2 at 5-10 mM in panning solutions helped to recover more plaque-forming units at least at round one of the screening. Subtractive docking analyses were designed by using a pool of common redundant peptides known as parasites. This rationale helped us differentiate between possibly specific and non-specific bindings. We found notable differences in docking characteristics between different sets of peptides either related to different targets or related to zinc-conditions. The set of zinc-related peptides shows advantageous docking profiles: sharper binding for some positions and distinct exclusive bound residues, including the relevant R248 and R273. Zinc would have modulating/helping role in the targeting of protein P53 by phage displayed peptides in addition to an enhancement action on bacterial infection.

molecular biology↗