Original Article

Exp Neurobiol 2016; 25(1): 24-32

Published online February 29, 2016

© The Korean Society for Brain and Neural Sciences

Agmatine Ameliorates High Glucose-Induced Neuronal Cell Senescence by Regulating the p21 and p53 Signaling

Juhyun Song1, Byeori Lee1, Somang Kang1,2, Yumi Oh1,2, Eosu Kim3, Chul-Hoon Kim4, Ho-Taek Song5 and Jong Eun Lee1,2*

1Department of Anatomy, Yonsei University College of Medicine, 2BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, 3Department of Psychiatry, Yonsei University College of Medicine, 4Department of Pharmacology, Yonsei University College of Medicine, 5Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul 03722, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-2228-1646, 1659, FAX: 82-2-365-0700

Received: February 1, 2016; Revised: February 12, 2016; Accepted: February 12, 2016


Neuronal senescence caused by diabetic neuropathy is considered a common complication of diabetes mellitus. Neuronal senescence leads to the secretion of pro-inflammatory cytokines, the production of reactive oxygen species, and the alteration of cellular homeostasis. Agmatine, which is biosynthesized by arginine decarboxylation, has been reported in previous in vitro to exert a protective effect against various stresses. In present study, agmatine attenuated the cell death and the expression of pro-inflammatory cytokines such as IL-6, TNF-alpha and CCL2 in high glucose in vitro conditions. Moreover, the senescence associated-β-galatosidase's activity in high glucose exposed neuronal cells was reduced by agmatine. Increased p21 and reduced p53 in high glucose conditioned cells were changed by agmatine. Ultimately, agmatine inhibits the neuronal cell senescence through the activation of p53 and the inhibition of p21. Here, we propose that agmatine may ameliorate neuronal cell senescence in hyperglycemia.

Keywords: Agmatine, High glucose, Hyperglycemia, Cell death, Senescence, Pro-inflammatory cytokines, p53, p21