Comparative Analysis of AGE and RAGE Levels in Human Somatic and Embryonic Stem Cells under H₂O₂‐Induced Noncytotoxic Oxidative Stress Conditions

Abstract

The accumulation of advanced glycation end products (AGEs) occurs in ageing and in many degenerative diseases as a final outcome of persistent oxidative stress on cells and organs. Environmental alterations taking place during early embryonic development can also lead to oxidative damage, reactive oxygen species (ROS) production, and AGE accumulation. Whether similar mechanisms act on somatic and embryonic stem cells (ESC) exposed to oxidative stress is not known; and therefore, the modelling of oxidative stress in vitro on human ESC has been the focus of this study. We compared changes in Nε-carboxymethyl-lysine (CML) advanced glycation end products and RAGE levels in hESC versus differentiated somatic cells exposed to H2O2 within the noncytotoxic range. Our data revealed that hESC accumulates CML and RAGE under oxidative stress conditions in different ways than somatic cells, being the accumulation of CML statistically significant only in somatic cells and, conversely, the RAGE increase exclusively appreciated in hESC. Then, following cardiac and neural differentiation, we observed a progressive removal of AGEs and at the same time an elevated activity of the 20S proteasome. We conclude that human ESCs constitute a unique model to study the consequence of an oxidative environment in the pluripotent cells of the embryo during the human preimplantation period.

PA28α overexpressing female mice maintain exploratory behavior and capacity to prevent protein aggregation in hippocampus as they age

“…Such mechanism could theoretically apply to humans as well, since deleterious protein damage (CML) has been shown to dramatically decrease also as human embryonic stem cells (hESCs) differentiate (Barandalla et al, 2017). However, no one has yet to our knowledge investigated PA28-20S proteasome activity during differentiation of hESCs.…”

“…Notably, the PA28αβ variant with chaperone‐like function is likely exclusively overrepresented in PA28αOE, and overexpression of the 20S proteasome activating PA28αβ may still affect proteostasis in a manner that could lead to prolonged life span. Such mechanism could theoretically apply to humans as well, since deleterious protein damage (CML) has been shown to dramatically decrease also as human embryonic stem cells (hESCs) differentiate (Barandalla et al, 2017). However, no one has yet to our knowledge investigated PA28‐20S proteasome activity during differentiation of hESCs.…”

Insulin-like Growth Factor-1 Receptor Dictates Beneficial Effects of Treadmill Training by Regulating Survival and Migration of Neural Stem Cell Grafts in the Injured Spinal Cord

“…Nitric oxide (NO)-associated radical species can kill transplanted NSCs in the injured spinal cord, and SIN-1 was used to produce RNS to damage cultured NSCs [26]. H 2 O 2 has been frequently used to induce oxidative stress in stem cells [2728]. Cultured NSCs were incubated in medium containing either SIN-1 or H 2 O 2 for 48 h with or without IGF-1 at a concentration of 20 ng/ml.…”

An Overview of the Posttranslational Modifications and Related Molecular Mechanisms in Diabetic Nephropathy

“…• Generation of AGEs promoted • Mangalmurti et al (2010), Delbin et al (2012), Lo et al (2015), and Barandalla et al (2017) • The renin-angiotensin system and expression of TGF-β, NF-κB, AP-1, and SP-1 dysregulated…”

“…of AGEs such as N-carboxymethyl-lysine and pentosidine, which consequently form an interaction loop between ROS and AGEs (Mangalmurti et al, 2010;Delbin et al, 2012;Lo et al, 2015;Barandalla et al, 2017). These events affect the renin-angiotensin system and regulate TGF-β, NF-κB, AP-1, and SP-1, which provokes abundant pro-inflammatory and profibrotic responses.…”