Abstract
Adipose-derived stem cells (ADSCs) play an important role in cell therapy and regenerative medicine. However, local nutritional deficiency often limits therapeutical effect of the transplanted cells. Acetyl l-carnitine (ALC) is a common energy metabolism regulator and free radical scavenger. This study investigated the effect of ALC on ADSCs exposed to severe serum-deprivation and explored the relative machanisms. Treating with 1 mM ALC improved proliferation and alleviated senescence of starved cells, accompanied with reduced reactive oxygen species (ROS) and increased protein expression of SOD1 and catalase. In addition, ALC inhibited apoptosis but increased starvation-induced autophagy, which might be related to the regulation of phases of dissociation of Bcl-2-Beclin1 and Bcl-2-Bax complexes. Evidence obtained by replacing ALC with N-acetylcysteine (N-AC) suggested that ROS might be the central inducer of autophagy, apoptosis and senescence. There was a difference between ALC and N-AC in the protection mechanism, that was, compared with N-AC, ALC maintained autophagy well at the same time as anti-oxidation. Inhibition of autophagy by 3-methyladenine (3-MA) partially offset the protective effect of ALC. However, despite low-level ROS and enhanced autophagy, ALC with high concentration (10 mM) markedly aggravated cell apoptosis and senescence, thus losing cytoprotection and even causing damage.
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The data used or analysed during the present study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors are grateful for the help and support given by Central Laboratory of First Affiliated Hospital of Wenzhou Medical University. This research was financially supported by National Natural Science Foundation of China (81971850) and Municipal Science and Technology Bureau of Wenzhou (Y2020085, Y20190017, Y20180148).
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This research was financially supproted by National Natural Science Foundation of China (81971850) and Municipal Science and Technology Bureau of Wenzhou (Y2020085, Y20190017, Y20180148).
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Conceptualization, YH and ML methodology, TP and YQ software, TL validation, ZZ and YH formal analysis, TP investigation, TP and YQ resources, JW data curation, LL writing-original draft preparation, TP and YQ writing-review and editing, YH, ML and LL.
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Pan, T., Qian, Y., Li, T. et al. Acetyl l-carnitine protects adipose-derived stem cells against serum-starvation: regulation on the network composed of reactive oxygen species, autophagy, apoptosis and senescence. Cytotechnology 74, 105–121 (2022). https://doi.org/10.1007/s10616-021-00514-y
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DOI: https://doi.org/10.1007/s10616-021-00514-y