Jeong, Eui Kyun BASKAR, SELVARAJ Clovis, Shyaka Son, Yun Jeong Park, Tae Hoo Veeramanoharan,Ashokkumar Kim, Hoe-In Yoo, Ki-Yeon Lee, Jae Wook Park, Chung-Min 2024-01-12T02:33:33Z 2024-01-12T02:33:33Z 2023-01-07 2023-01 0891-5849 https://pubs.kist.re.kr/handle/201004/75859 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. English Elsevier BV Synthesis and neuroprotective effects of H2S-donor-peptide hybrids on hippocampal neuronal cells Article 10.1016/j.freeradbiomed.2022.12.012 1 Free Radical Biology and Medicine, v.194, pp.316 - 325 Free Radical Biology and Medicine 194 316 325 N scie scopus 000906923000001 Biochemistry & Molecular Biology Endocrinology & Metabolism Biochemistry & Molecular Biology Endocrinology & Metabolism Article HYDROGEN-SULFIDE PROTECTS ANXIOLYTIC-LIKE ACTIVITY NOSH-ASPIRIN NBS-1120 OXIDATIVE STRESS CHEMICAL BIOLOGY NITRIC-OXIDE BRAIN-INJURY IN-VITRO ACTIVATION ISCHEMIA Oxidative stress Hydrogen sulfide Tripeptide Neuroprotective effect ROS