Photoinduced Upregulation of Calcitonin Gene-Related Peptide in A549 Cells through HNO Release from a Hydrophilic Photocontrollable HNO Donor

Abstract

Nitroxyl (HNO), a one-electron-reduced form of nitric oxide, has various biological activities, including a cardioprotective effect. Here, we first synthesized another, more hydrophilic photocontrollable HNO donor (3), which can release HNO in a spatially and temporally controlled manner, and then examined the properties of our series of compounds as practical HNO donors in a cellular system under photocontrol. We selected compound 2 as the preferred donor, and used it to show that calcitonin gene-related peptide (CGRP) can be upregulated in A549 cells via photocontrolled HNO release. This result demonstrates the suitability of this photocontrollable HNO donor for biological investigations.

Controlled release of HNO from chemical donors for biological applications

“…However, A549 cells have been reported to produce CGRP in response to IL-1beta stimulation [40]. In addition, exogenous HNO treatment was confirmed to induce CGRP upregulation in vitro, using Angeli's salt [39] (Fig. 1).…”

“…Compound B was indeed found to be applicable for experiments to investigate CGRP upregulation at the cellular level [39].…”

Photocontrol of NO, H₂S, and HNO Release in Biological Systems by Using Specific Caged Compounds

“…The alkyl group at the 9 and 10 positions of anthracene served to stabilize the DielsAlder adduct thermally, and we added the nitroaryl group to an acylnitroso moiety to facilitate absorption in the UVA region. Based on this molecular design, we synthesized a candidate HNO releaser, NiP-DAC-DA 27,28) (Fig. 1, 6).…”

“…NiP-DAC-DA was also shown to be applicable for cellular experiments. 28) For example, in several cell lines, such as A549, HNO induces calcitonin gene-related peptide, CGRP, a neuropeptide that exhibits vasodilatory, ionotropic and chronotropic activities via induction of cAMP. 19) We then examined whether CGRP was induced in A549 cells treated with NiP-DAC-DA upon photoirradiation, by means of enzyme immunoassay (EIA).…”

“…The hetero Diels-Alder adduct-type structure might be hard to stabilize thermodynamically, so it may be better to seek another caging (parametric, n=3-6). 28) method for acylnitroso compounds.…”