Jeffrey B. Travers, M.D., Ph.D. (Advisor); Michael G. Kemp, Ph.D. (Committee Member); Ravi P. Sahu, Ph.D. (Committee Member)
Master of Science (MS)
In skin connective tissue, dermal fibroblasts appear to be the most prevalent cell type. They are in charge of making the extracellular matrix that makes up the skin's connective tissue, and also involved in wound healing. Moreover, they produce Insulin-like growth factor-1 (IGF-1) which helps in activation of Insulin growth factor-1 receptor (IGF-1R). This receptor helps to control cell proliferation and responses to DNA-damaging substances such as UVB radiation, reactive oxygen species (ROS), and therapeutic drugs. According to our findings, lack of IGF-1 expression in the dermis of elderly patients due to fibroblast senescence (senescence is characterized by which cells enter a condition of irreversible growth arrest after irreversibly avoiding dividing without enduring cell death) has been linked to an increased incidence of skin cancer in the epidermal keratinocyte. Our group resolved that pretreatment with creatine monohydrate and nicotinamide shows a protective effect on oxidative-stress senescence. Based on this study, the present project was designed to study the effect of creatine and nicotinamide on stress-induced reactive oxygen species (ROS) generation as a possible mechanism for their protective effects. Similarly, the present study also examined how the pro-energetics acts on senescence as a post-treatment. Using primary human dermal fibroblasts exposed to H2O2 in vitro, via ROS staining, beta-galactosidase staining, and RT-qPCR, we discovered that pre-treatment with creatine and nicotinamide reduces oxidative stress-induced ROS levels, while post-treatment with creatine or nicotinamide after H2O2 had no effect on stress-induced senescence.
Department or Program
Department of Pharmacology and Toxicology
Year Degree Awarded
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