Tri-substituted organotin compounds, but not retinoic acid, are potent ligands of complement component 8 γ.

Tri-substituted organotin compounds, but not retinoic acid, are potent ligands of complement component 8 γ. J Toxicol Sci. 2020;45(9):581-587 Authors: Yamamoto K, Hiromori Y, Matsumaru D, Ishii Y, Takeshita Y, Tsubakihara I, Kimura T, Nagase H, Nakanishi T Abstract Complement component 8 γ (C8γ) is a subunit of complement protein 8 (C8), which itself is a subunit of the complement cytolytic membrane attack complex. However, C8γ is also suggested to be a carrier protein for the general clearance of endogenous and exogenous compounds because it belongs to the lipocalin family of small secreted proteins that have the common ability to bind small hydrophobic ligands. Although retinoic acid, a metabolite of vitamin A, has been suggested as a potential ligand of C8γ, it remains unclear which other substances are able to bind to C8γ as ligands. Here, we evaluated the binding affinity of several organotin compounds that are ligands of a receptor of retinoic acid, retinoid X receptor, by using radioligand binding assays. The amount of [14C]triphenyltin (TPT), a tri-substituted organotin, that bound to purified recombinant C8γ was increased with increasing protein concentration, whereas that of [3H]all-trans retinoic acid and [3H]9-cis retinoic acid was unchanged. Scatchard analysis revealed that [14C]TPT bound to C8γ with an equilibrium dissociation constant (Kd) of 56.2 ± 16.2 nM. Non-radiolabeled tributyltin (TBT), another tri-subs...
Source: Journal of Toxicological Sciences - Category: Toxicology Tags: J Toxicol Sci Source Type: research