Molecular mechanism underlying modulation of TRPV1 heat activation by polyols.

Sensing noxiously high temperatures is crucial for living organisms to avoid heat-induced injury. The TRPV1 channel has long been known as a sensor for noxious heat. However, the mechanism of how this channel is activated by heat remains elusive. Here we found that a series of polyols including sucrose, sorbitol, and hyaluronan significantly elevate the heat activation threshold temperature of TRPV1. The modulatory effects of these polyols were only observed when they were perfused extracellularly. Interestingly, mutation of residues E601 and E649 in the outer pore region of TRPV1 largely abolished the effects of these polyols. We further observed that intraplantar injection of polyols into the hind paws of rats reduced their heat-induced pain response. Our observations not only suggest that the extracellular regions of TRPV1 are critical for the modulation of heat activation by polyols, but also indicate a potential role of polyols in reducing heat-induced pain sensation.

The role of Piezo1 in conventional aqueous humor outflow dynamics.

Controlling intraocular pressure (IOP) remains the mainstay of glaucoma therapy. The trabecular meshwork (TM), the key tissue responsible for aqueous humor (AH) outflow and IOP maintenance, is very sensitive to mechanical forces. However, it is not understood whether Piezo channels, very sensitive mechanosensors, functionally influence AH outflow. Here, we characterize the role of Piezo1 in conventional AH outflow. Immunostaining and western blot analysis showed that Piezo1 is widely expressed by TM. Patch-clamp recordings in TM cells confirmed the activation of Piezo1-derived mechanosensitive currents. Importantly, the antagonist GsMTx4 for mechanosensitive channels significantly decreased steady-state facility, yet activation of Piezo1 by the specific agonist Yoda1 did not lead to a facility change. Furthermore, GsMTx4, but not Yoda1, caused a significant increase in ocular compliance, a measure of the eye's transient response to IOP perturbation. Our findings demonstrate a potential role for Piezo1 in conventional outflow, likely under pathological and rapid transient conditions.

Structural characterization and proliferation activity of chondroitin sulfate from the sturgeon, Acipenser schrenckii.

The cartilages of marine fish, such as sharks and sturgeon, are important resources of the bioactive chondroitin sulfate (CS). To explore glycosaminoglycans from marine fish, polysaccharides from the cartilage of the sturgeon, Acipenser schrenckii, were extracted. Using enzyme-assisted extraction and anion-exchange chromatography, an uronic acid-containing polysaccharide, YG-1, was isolated. YG-1 is composed of GlcN, GlcUA, GalN, and Gal, in the ratio of 1.4: 3.4: 3.7: 1.0, and its molecular weight was determined to be 3.0 × 105 Da. YG-1 was confirmed to be chondroitin 4-sulfate (CS) composed of →4GlcAß1→3GalNAc4Sß1→ and minor →4GlcAß1→3GalNAcß1→, which was confirmed using IR spectroscopy, disaccharide composition analysis, and NMR. Bioactivity studies, including MTT assay and scratch-wound assays revealed that CS from Acipenser schrenckii had significant proliferation activity. The proliferation activity of the polysaccharide, YG-1, was related to Fibroblast growth factor 2 (FGF2). GalNAc 4S of YG-1 could be the binding sites of FGF2 and FGFR.