ABSTRACT
Hydrogen sulfide (H2S) has emerged as an endogenous signaling molecule that functions in many physiological and pathological processes of human cells in health and disease, including neuromodulation and neuroprotection, inflammation, angiogenesis, and vasorelaxation. The limited clinical applications of current H2S donors have led to the development of H2S donor hybrid compounds that combine current H2S donors with bioactive molecules. Finely tuned multi-targeting hybrid molecules have been shown to have complementary neuroprotective effects against reactive oxygen species (ROS)-induced oxidative stress. In this study, we developed hybrid molecules combining a dithiolethione-based slow-releasing H2S donor that exerts neuroprotective effects, with the tripeptides glycyl-L-histidyl-l-lysine (GHK) and L-alanyl-L-cystinyl-l-glutamine (ACQ), two natural products that exhibit powerful antioxidant effects. In particular, a hybrid combination of a dithiolethione-based slow-releasing H2S donor and ACQ exhibited significant neuroprotective effects against glutamate-induced oxidative damage in HT22 hippocampal neuronal cells. This hybrid remarkably suppressed Ca2+ accumulation and ROS production. Furthermore, it efficiently inhibited apoptotic neuronal cell death by blocking apoptosis-inducing factor release and its translocation to the nucleus. These results indicate that the hybrid efficiently inhibited apoptotic neuronal cell damage by complementary neuroprotective actions.
Subject(s)
Hydrogen Sulfide , Neuroprotective Agents , Humans , Neuroprotective Agents/pharmacology , Reactive Oxygen Species/metabolism , Oxidative Stress , Peptides/pharmacology , Hippocampus/metabolism , Hydrogen Sulfide/metabolismABSTRACT
The aim of this study is to evaluate the feasibility of hyaluronic acid/sodium alginate (HA/SA) scaffold-based interpenetrating polymeric network (IPN) for the proliferation and chondrogenic differentiation of the human adipose-derived stem cells (hADSCs). The hADSCs cultured in HA/SA IPN scaffold exhibited enhanced cell adhesion and proliferation compared to the HA scaffold. Superior chondrogenic differentiation of hADSCs in HA/SA IPN scaffold, compared to HA-based scaffold, was confirmed by measuring expression levels of chondrogenic markers. These results suggested that HA/SA IPN scaffold could provide a desirable environment for the cell adhesion, proliferation and chondrogenic differentiation of hADSCs.
