Aromatic Fluorination of Multiblock Amphiphile Enhances Its Incorporation into Lipid Bilayer Membranes
CHEMISTRYOPEN
Authors: Sasaki, Ryo; Sato, Kohei; Kinbara, Kazushi
Abstract
We designed multiblock amphiphiles AmF and AmH, which consist of perfluorinated and non-fluorinated hydrophobic units, respectively. Absorption spectroscopy revealed that both amphiphiles are molecularly dispersed in organic solvent, while they form aggregates under aqueous conditions. Furthermore, we investigated whether AmF and AmH can be incorporated into DOPC lipid bilayer membranes, and found that the maximum concentration of AmF that can be incorporated into DOPC lipid bilayer membranes is 43 times higher than that of AmH.
The P450 side-chain cleavage enzyme Cyp11a2 facilitates steroidogenesis in zebrafish
JOURNAL OF ENDOCRINOLOGY
Authors: Li, Nan; Oakes, James A.; Storbeck, Karl-Heinz; Cunliffe, Vincent T.; Krone, Nils P.
Abstract
Cytochrome P450 side-chain cleavage enzyme, encoded by the CYP11A1 gene, catalyzes the first and rate-limiting step of steroid hormone biosynthesis. Previous morpholino-knockdown studies in zebrafish suggested cyp11a2 is a functional equivalent of human CYP11A1 and is essential for interrenal steroidogenesis in zebrafish larvae. The role of Cyp11a2 in adult zebrafish, particularly in gonadal steroidogenesis, remains elusive. To explore the role of Cyp11a2 in adults, we developed zebrafish mutant lines by creating deletions in cyp11a2 using the CRISPR/Cas9 genomic engineering approach. Homozygous cyp11a2 mutant zebrafish larvae showed an upregulation of the hypothalamic-pituitary-interrenal axis. Furthermore, these Cyp11a2-deficient zebrafish demonstrated profound glucocorticoid and androgen deficiencies. Cyp11a2 homozygotes only developed into males with feminized secondary sex characteristics. Adult cyp11a2(-/-) mutant fish showed a lack of natural breeding behaviors. Histological characterization revealed disorganized testicular structure and significantly decreased numbers of mature spermatozoa. These findings are further supported by the downregulation of the expression of several pro-male genes in the testes of cyp11a2 homozygous zebrafish, including sox9a, dmrt1 and amh. Moreover, the spermatogonia markers nanos2 and piwil1 were upregulated, while the spermatocytes marker sycp3 and spermatids marker odf3b were downregulated in the testes of cyp11a2 homozygous mutants. Our expression analysis is consistent with our histological studies, suggesting that spermatogonia are the predominant cell types in the testes of cyp11a2 homozygous mutants. Our work thus demonstrates the crucial role of Cyp11a2 in interrenal and gonadal steroidogenesis in zebrafish larvae and adults.