Can blood components with age-related changes influence the ageing of endothelial cells?
Research on vascular endothelial cell ageing helps elucidate the pathogenesis of diseases associated with cell ageing. To investigate endothelial senescence, we used 2-DE coupled with MS to perform a proteomic analysis of: (i) peripheral blood mononuclear cells (PBMCs) from donors in their 20 s ('young') or 60 s ('old') and (ii) human dermal microvascular endothelial cells (HDMECs) treated with sera from young and old donors. Identified proteins could be classified into several functional categories: (i) cytoskeletal regulators: CapG and cofilin 1; (ii) stress response and signal pathway proteins: TXNDC5 and RSU-1; and (iii) apoptosis proteins: Annexin V. We confirmed by Western blot a decrease of RSU-1, CapG and TXNDC5 in PBMCs from old donors. RSU-1, which regulates signal transduction of the downstream Ras, showed decreased mRNA and protein levels in PBMCs from old donors and decreased mRNA levels in HDMECs treated with sera from old donors. In addition, Ras protein levels were increased in PBMCs from old donors. These data indicate that reduced RSU-1 might induce Ras expression, which subsequently could provoke Ras-induced senescence. In conclusion, our data suggest that blood components that exhibit age-related changes, such as alterations in cytoskeletal regulators and stress proteins, may be associated with endothelial cell ageing.
Noh
Ji Yeon
JY
Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Oh
Sang Ho
SH
Lee
Ju Hee
JH
Kwon
Yeon Sook
YS
Ryu
Dong Jin
DJ
Lee
Kwang Hoon
KH
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood* / Q000502:physiology*; D017304:Annexin A5 / Q000378:metabolism; D015153:Blotting, Western; D016922:Cellular Senescence / Q000502:physiology*; D051338:Cofilin 1 / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D014746:Vimentin / Q000378:metabolism; D055815:Young Adult
D000199:Actins; D017304:Annexin A5; D051338:Cofilin 1; D029721:Drosophila Proteins; C087940:LRPPRC protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011506:Proteins; D014157:Transcription Factors; D014746:Vimentin; C495946:ics protein, Drosophila; C066575:CAPG protein, human; D016283:Proto-Oncogene Proteins p21(ras); D019704:Protein Disulfide-Isomerases; C480743:TXNDC5 protein, human