Nitrosylation of Tissue Transglutaminase enhances fibroblast migration and regulates MMP activation

In wound healing, the TG2 enzyme plays a dual functional role. TG2 has been shown to regulate extracellular matrix (ECM) stabilization by its transamidase activity while increasing cell migration by acting as a cell adhesion molecule. In this process, nitric oxide (NO) plays a particularly important role by nitrosylation of free cysteine ​​residues on TG2, leading to the irreversible inactivation of the catalytic activity. In this study, transfected fibroblasts expressing TG2 under the control of the tetracycline-off promoter were treated with NO donor S-nitroso-N-acetyl penicillamine (SNAP) to analyze the interplay between NO and TG2 in the regulation of cell migration/invasion as well as TGF-β1-dependent MMP activation. Our results demonstrated that inhibition of TG2 cross-linking activity by SNAP promoted the migration and invasion capacity of fibroblasts by hindering TG2-mediated TGF-β1 activation. While the inhibition of TG2 activity by NO downregulated the biosynthesis and activity of MMP-2 and MMP-9, that of MMP-1a and MMP-13 was shown to be upregulated in a TGF-β1-dependent manner under the same conditions. In the presence of SNAP, interaction of TG2 with its cell surface binding partners Integrin-β1 and Syndecan-4 was reduced, which was paralleled by an increase in TG2 and PDGF association. These findings suggests that migratory phenotype of fibroblasts can be regulated by the interplay between nitric oxide and TG2 activity

A multifunctional key to open a new window on the path to natural resources-lessons from a study on chemical composition and biological capability of Paeonia mascula L. from Turkey

The genus Paeonia has gained great interest from the scientific community for exploration as a source of bioactive compounds. The current work focused on the chemical characterisation and biological properties of Paeonia mascula L. from Turkey. The chemical characterisation of the extracts was analysed by LC-DAD-ESI and LC-APCI-MS. The antioxidant, enzyme inhibitory and anticancer properties were evaluated in vitro. The methanol extract was the most effective as antioxidant, metal chelator and was the most effective inhibitor of acetylcholinesterase (AChE) and tyrosinase. The chloroform extract showed highest inhibition of butrylcholinesterase (BChE) and amylase. Ethyl acetate extract displayed glucosidase inhibition. The most abundant compounds were hexagalloyl glucose, penta galloyl glucose, gallic acid, tetragalloyl glucose, paeoniflorin and the most abundant flavonoid was quercetin-3-O-glucoside. β-sitosterol was the most abundant phytosterol. The anticancer effect of P. mascula was evaluated by using HELA cells evaluating different pathways. The possible inhibition effect of P. mascula on the reactive oxygen species (ROS) pathway was controlled by performing the advanced glycation end product (AGE). To determine the effect of P. mascula on active molecular pathways in the HELA cancer cell line, the levels of Phospho-NF-Kβ p65, AGE receptor RAGE protein, antiapoptotic BCL-2, proapoptotic BAX and P-53 proteins were checked, respectively. Phospho-NF-Kβ p65, RAGE and BCL-2, which are both ROS inducers and play an active role in cancer prognosis, were found to have decreased levels after the application of P. mascula. Our findings provide a scientific basis for Paeonia mascula, which may serve as a source of naturally occurring bioactive compounds for healthpromoting applications