Angiopoietin-1 reduces H(2)O(2)-induced increases in reactive oxygen species and oxidative damage to skin cells.
UV light-based damage to skin cells can cause photoaging and skin cancer. A major cause of UV light-induced damage to skin is increased free radicals, such as superoxides. Increased superoxides can cause oxidative and nitrative damage to cell components. Thus, agents that counteract these damages may have therapeutic value. Herein, we show that angiopoietin-1 (ang1) prevented and blocked H(2)O(2)-induced increases in superoxides in human spontaneously immortalized keratinocyte line, HaCaT, and primary melanocytes (HeMn). Ang1 prevented H(2)O(2)-induced increases in damage to DNA (8-hydroxy-2'-deoxyguanosine) and proteins (nitrotyrosinylation). Ang1 promoted skin cell metabolism/viability, adhesion, and akt and MAPK(p42/44) activations. Using multi-gene transcriptional profiling, we found that skin cells express integrin subunits {(beta(1), beta(4-6), beta(8), alpha(v), alpha(2), alpha(3), alpha(6) (HaCaT)), (beta(1), beta(3), beta(5), beta(8), alpha(v), alpha(3) (HeMn))} and lack tie2 receptor mRNA. Integrin antibodies (alpha(v), beta(1)) disrupted skin cell adhesion to ang1 and ang1-induced decreases in superoxides. Our findings show that ang1 blocks free radical damage to skin cells and may be clinically useful to prevent and/or reduce photoaging and skin cancer.
Ismail
Nesreen S
NS
Vascular Biology Program, Children's Hospital Boston, Boston, Massachusetts, USA.
Pravda
Elke A
EA
Li
Dan
D
Shih
Shou-Ching
SC
Dallabrida
Susan M
SM
D042683:Angiopoietin-1 / Q000378:metabolism / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004249:DNA Damage / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D016023:Integrins / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects* / Q000502:physiology; D012878:Skin Neoplasms / Q000378:metabolism / Q000517:prevention & control; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D016023:Integrins; D016877:Oxidants; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3