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Knockdown of paraoxonase 1 expression influences the ageing of human dermal microvascular endothelial cells
Author(s) -
Lee Yun Sun,
Park Chang Ook,
Noh Ji Yeon,
Jin Shan,
Lee Na Ra,
Noh Seongmin,
Lee Ju Hee,
Lee Kwang Hoon
Publication year - 2012
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2012.01555.x
Subject(s) - gene knockdown , ageing , paraoxonase , microbiology and biotechnology , chemistry , medicine , biology , oxidative stress , biochemistry , gene
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 ( PON 1) was selected in this study. To elucidate the role of PON 1 on skin ageing and determine how it controls cellular senescence, the characteristics of PON 1 in human dermal microvascular endothelial cells ( HDMEC s) were determined. When the expression of endogenous PON 1 was knocked‐down by small interfering RNA (si RNA ) targeting PON 1, HDMEC s 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 PON 1 si RNA ‐treated HDMEC s was higher than that in scrambled si RNA ‐treated HDMEC s. In addition, the expressions of moesin and rho GTP dissociation inhibitor, additional age‐related candidate biomarkers, were decreased by PON 1 knock‐down in HDMEC s. In conclusion, these results suggest that PON 1 functions as an ageing‐related protein and plays an important role in the cellular senescence of HDMEC s.