Substance-P Restores Cellular Activity of ADSC Impaired by Oxidative Stress

Abstract

Oxidative stress induces cellular damage, which accelerates aging and promotes the development of serious illnesses. Adipose-derived stem cells (ADSCs) are novel cellular therapeutic tools and have been applied for tissue regeneration. However, ADSCs from aged and diseased individuals may be affected in vivo by the accumulation of free radicals, which can impair their therapeutic efficacy. Substance-P (SP) is a neuropeptide that is known to rescue stem cells from senescence and inflammatory attack, and this study explored the restorative effect of SP on ADSCs under oxidative stress. ADSCs were transiently exposed to H2O2, and then treated with SP. H2O2 treatment decreased ADSC cell viability, proliferation, and cytokine production and this activity was not recovered even after the removal of H2O2. However, the addition of SP increased cell viability and restored paracrine potential, leading to the accelerated repopulation of ADSCs injured by H2O2. Furthermore, SP was capable of activating Akt/GSK-3β signaling, which was found to be downregulated following H2O2 treatment. This might contribute to the restorative effect of SP on injured ADSCs. Collectively, SP can protect ADSCs from oxidant-induced cell damage, possibly by activating Akt/GSK-3β signaling in ADSCs. This study supports the possibility that SP can recover cell activity from oxidative stress-induced dysfunction.

Metformin attenuates H2O2‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

“…The targeted treatment of osteoblasts or osteoclasts is limited, and the systemic regulation of osteoporosis is the focus of further studies. Oxidative stress is regarded as the main factor leading to body aging and organ damage (26)(27)(28). Studies have indicated that postmenopausal women generally have reduced antioxidant capacity and are in a highly oxidized state (29,30).…”

Substance-P Inhibits Cardiac Microvascular Endothelial Dysfunction Caused by High Glucose-Induced Oxidative Stress

“…SP has been previously reported to protect cell apoptosis against inflammation or oxidative stress in the retina and adipose stem cells [25][26][27], and the systemic administration of SP has been shown to relieve diabetic complications in preclinical studies [28]. However, its mechanism of action on the endothelium has not yet been elucidated.…”

“…This function can accelerate tissue repair by promoting the participation of stem cells in wound healing. Moreover, SP can protect diverse types of cells against inflammation or oxidative stress by preserving cell viability and blocking cellular alterations [25][26][27]. The treatment of acute inflammatory disease with SP ameliorates excessive inflammation by increasing the number of M2 macrophages and regulatory T cells in the circulation and lymphoid organs, which reduces disease severity [28][29][30][31][32][33].…”

Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action

“…Melatonin exerts a similar effect on Nrf2, facilitating its nuclear translocation, in the presence of oxidative stress (Das et al 2020 ). Likewise, Park et al, 2020 demonstrated that the addition of substance-P (SP) increased cell viability, supporting the possibility that SP can recover cell activity after oxidative stress-induced dysfunction (Park et al 2020 ). Based on this, it could be said that there are certain substances, including melatonin, that could recover the cellular redox potential, altered by oxidative stress, preventing apoptosis.…”