P-Glycoprotein Inhibitor Tariquidar Plays an Important Regulatory Role in Pigmentation in Larval Zebrafish

Abstract

Zebrafish has emerged as a powerful model in studies dealing with pigment development and pathobiology of pigment diseases. Due to its conserved pigment pattern with established genetic background, the zebrafish is used for screening of active compounds influencing melanophore, iridophore, and xanthophore development and differentiation. In our study, zebrafish embryos and larvae were used to investigate the influence of third-generation noncompetitive P-glycoprotein inhibitor, tariquidar (TQR), on pigmentation, including phenotype effects and changes in gene expression of chosen chromatophore differentiation markers. Five-day exposure to increasing TQR concentrations (1 µM, 10 µM, and 50 µM) resulted in a dose-dependent augmentation of the area covered with melanophores but a reduction in the area covered by iridophores. The observations were performed in three distinct regions—the eye, dorsal head, and tail. Moreover, TQR enhanced melanophore renewal after depigmentation caused by 0.2 mM 1-phenyl-2-thiourea (PTU) treatment. qPCR analysis performed in 56-h post-fertilization (hpf) embryos demonstrated differential expression patterns of genes related to pigment development and differentiation. The most substantial findings include those indicating that TQR had no significant influence on leukocyte tyrosine kinase, GTP cyclohydrolase 2, tyrosinase-related protein 1, and forkhead box D3, however, markedly upregulated tyrosinase, dopachrome tautomerase and melanocyte inducing transcription factor, and downregulated purine nucleoside phosphorylase 4a. The present study suggests that TQR is an agent with multidirectional properties toward pigment cell formation and distribution in the zebrafish larvae and therefore points to the involvement of P-glycoprotein in this process.

Anti-Melanogenic Effects of Takifugu flavidus Muscle Hydrolysate in B16F10 Melanoma Cells and Zebrafish

“…Pigmentation in the eyes and dorsal regions was lighter and displayed a spotted distribution pattern, as opposed to the darker, uniformly distributed pigment observed in the control group. Typically, zebrafish embryos are cultured in a medium containing PTU, a highly effective sulfur-based TYR inhibitor, to inhibit melanin production [43]. Our findings indicated that both TFMH and T-6 significantly reduced melanin content and TYR activity in zebrafish, with their inhibitory effects intensifying with increasing concentrations.…”

Artificial Intelligence-Assisted Optimization of Antipigmentation Tyrosinase Inhibitors: De Novo Molecular Generation Based on a Low Activity Lead Compound

“…Zebrafish share a genetic similarity of 87% with humans, and their melanin synthesis mechanism closely resembles that of humans. , The genes involved in melanocyte regulation in zebrafish are well conserved with those in humans. , Additionally, the transparent skin of zebrafish embryos and larvae allows for convenient in vivo imaging and monitoring of melanin changes, making zebrafish an ideal model for studying melanocyte development and pigmentary disorders. Wild-type (AB) zebrafish (6 hpf) were used to evaluate the minimal toxic concentration (MTC) of compounds T0 and T3 , as well as kojic acid (Table ).…”

The Inhibitory Effect of Selected D2 Dopaminergic Receptor Agonists on VEGF-Dependent Neovascularization in Zebrafish Larvae: Potential New Therapy in Ophthalmic Diseases

“…All steps of reverse transcription were assessed according to the manufacturers’ protocols. qPCR was performed using SYBR Green (SYBR Select Master Mix, Applied Biosystems, Foster City, CA, USA) on a 7500 Fast Real-Time PCR System instrument (Applied Biosystems, Foster City, CA, USA) under previously described conditions [ 14 ]. Oligonucleotide primers were selected to detect: vascular endothelial growth factor Aa ( vegfaa ), vascular endothelial growth factor receptor 1 ( vegfr1 ), vascular endothelial growth factor receptor 2 ( vegfr2 ), placental growth factor a ( pgfa ), placental growth factor b ( pgfb ), fibroblast growth factor 2 ( fgf2 ), transforming growth factor-beta 1 ( tgfb1 ), insulin growth factor 2a ( igf2a ) and insulin growth factor 2b ( igf2b ).…”