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Knockdown of paraoxonase 1 expression influences the ageing of human dermal microvascular endothelial cells.

 Yun Sun Lee  ;  Chang Ook Park  ;  Ji Yeon Noh  ;  Shan Jin  ;  Na Ra Lee  ;  Seongmin Noh  ;  Ju Hee Lee  ;  Kwang Hoon Lee 
 EXPERIMENTAL DERMATOLOGY, Vol.21(9) : 682-687, 2012 
Journal Title
Issue Date
Adult ; Aged ; Aging/genetics ; Aging/metabolism ; Aryldialkylphosphatase/drug effects ; Aryldialkylphosphatase/genetics* ; Aryldialkylphosphatase/metabolism* ; Biomarkers/metabolism ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Endothelial Cells/metabolism* ; Endothelial Cells/pathology ; Gene Knockdown Techniques ; Humans ; Microfilament Proteins/metabolism ; Microvessels/metabolism ; Middle Aged ; RNA, Small Interfering/pharmacology ; Skin/blood supply ; Skin/metabolism* ; Skin Physiological Phenomena/drug effects ; Skin Physiological Phenomena/genetics ; Transfection ; Young Adult ; beta-Galactosidase/metabolism ; rho-Specific Guanine Nucleotide Dissociation Inhibitors/metabolism
ageing ; human dermal microvascular endothelial cell ; paraoxonase 1 ; plasma
Skin is one of the most commonly studied tissues for microcirculation research owing to its close correlation of cutaneous vascular function, ageing and age-related cardiovascular events. To elucidate proteins that determine this correlation between endothelial cell function and ageing in the vascular environment of the skin, we performed a proteomic analysis of plasma samples from six donors in their 20s (young) and six donors in their 60s (old). Among identified proteins, paraoxonase 1 (PON1) was selected in this study. To elucidate the role of PON1 on skin ageing and determine how it controls cellular senescence, the characteristics of PON1 in human dermal microvascular endothelial cells (HDMECs) were determined. When the expression of endogenous PON1 was knocked-down by small interfering RNA (siRNA) targeting PON1, HDMECs showed characteristic features of cellular senescence such as increases in senescence-associated β-galactosidase stained cells and enlarged and flattened cell morphology. At 48 h post-transfection, the protein expression of p16 in PON1 siRNA-treated HDMECs was higher than that in scrambled siRNA-treated HDMECs. In addition, the expressions of moesin and rho GTP dissociation inhibitor, additional age-related candidate biomarkers, were decreased by PON1 knock-down in HDMECs. In conclusion, these results suggest that PON1 functions as an ageing-related protein and plays an important role in the cellular senescence of HDMECs.
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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Jin, Shan(김산)
Park, Chang Ook(박창욱) ORCID logo https://orcid.org/0000-0003-3856-1201
Lee, Kwang Hoon(이광훈)
Lee, Na Ra(이나라)
Lee, Yun Sun(이윤선)
Lee, Ju Hee(이주희) ORCID logo https://orcid.org/0000-0002-1739-5956
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