Identification of sodium channel toxins from marine cone snails of the subgenera Textilia and Afonsoconus.

Voltage-gated sodium (NaV) channels are transmembrane proteins that play a critical role in electrical signaling in the nervous system and other excitable tissues. µ-Conotoxins are peptide toxins from the venoms of marine cone snails (genus Conus) that block NaV channels with nanomolar potency. Most species of the subgenera Textilia and Afonsoconus are difficult to acquire; therefore, their venoms have yet to be comprehensively interrogated for µ-conotoxins. The goal of this study was to find new µ-conotoxins from species of the subgenera Textilia and Afonsoconus and investigate their selectivity at human NaV channels. Using RNA-seq of the venom gland of Conus (Textilia) bullatus, we identified 12 µ-conotoxin (or µ-conotoxin-like) sequences. Based on these sequences we designed primers which we used to identify additional µ-conotoxin sequences from DNA extracted from historical specimens of species from Textilia and Afonsoconus. We synthesized six of these µ-conotoxins and tested their activity on human NaV1.1-NaV1.8. Five of the six synthetic peptides were potent blockers of human NaV channels. Of these, two peptides (BuIIIB and BuIIIE) were potent blockers of hNaV1.3. Three of the peptides (BuIIIB, BuIIIE and AdIIIA) had submicromolar activity at hNaV1.7. This study serves as an example of the identification of new peptide toxins from historical DNA and provides new insights into structure-activity relationships of µ-conotoxins with activity at hNaV1.3 and hNaV1.7.

Glutathione as a photo-stabilizer of avobenzone: an evaluation under glass-filtered sunlight using UV-spectroscopy.

Avobenzone is the most widely used UVA filter in sunscreen lotion and it is prone to degradation in the presence of sunlight/UV radiation. To overcome the photo-instability of avobenzone, various photostabilizers have been used as additives, including antioxidants such as vitamin C, vitamin E, and ubiquinone. In the present study, the well known antioxidant, glutathione, was evaluated for protecting avobenzone from photodegradation in the presence of glass-filtered sunlight. The features of glutathione as a skin whitener and a radical scavenger in cells have prompted the assessment of the photostabilzing activity of glutathione on avobenzone. Glutathione significantly attenuated the glass-filtered sunlight-induced degradation of avobenzone at equimolar or higher ratios of glutathione and avobenzone. Mutational studies have been undertaken to investigate the role of the thiol group and the isopeptide bond of glutathione on its photoprotection activity towards avobenzone. The thiol group of glutathione plays a vital role in exhibiting the photoprotection activity, which was further supported by the studies on photodegradation of avobonzone in the presence of ß-mercaptoethanol. The dual role of glutathione as a skin whitening agent and a photostabilizer of avobenzone may be useful for the development of multipurpose cosmetic lotions.