Angiopoietin-1 Reduces H2O2-Induced Increases in Reactive Oxygen Species and Oxidative Damage to Skin Cells

作者：Ismail Nesreen S; Pravda Elke A; Li Dan; Shih Shou Ching; Dallabrida Susan M^*

来源：Journal of Investigative Dermatology, 2010, 130(5): 1307-1317.

DOI：10.1038/jid.2009.431

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 H2O2-induced increases in superoxides in human spontaneously immortalized keratinocyte line, HaCaT, and primary melanocytes (HeMn). Ang1 prevented H2O2-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.

• 出版日期2010-5