Proteomic Alterations in Human Dermal Fibroblasts under Photo-Induced Pollution Caused by Excessive Solar Irradiations such as Infra-Red, Blue Light, UVA and UVB

Background: The skin serves as the first line of defense for the human body. Direct sunlight contains damaging radiations that can speed up the ageing process of the skin, resulting in wrinkles, leathery skin, dark patches, and solar elastosis. Objectives: To evaluate the effect of multiple solar irradiation related factors at the protein level in human dermal fibroblast (HDF). The overall effect of individual solar irradiations such as Infrared A (IRA), blue light (BL), UVA, and UVB on HDF cells and the extent of molecular level aberrations to be assessed and compared against each. Methods: Label-free quantitative proteomics (MS/MS) approach has been adopted in this study to observe the protein level changes induced in the HDF cells through various exposures of full light sources. Following that, downstream insilico analysis has been carried out. Results: In this study, it is demonstrated all the four different solar irradiations significantly contribute to the molecular degeneration of skin cells through various mechanisms. This study confirms that BL down-regulates DNA repair proteins and the skin cells-HDF stimulate the histone proteins as a response mechanism to maintain the chromosomal integrity. Conclusions: The proteomics experiment carried out in the current study intends to support the future sun care products based on full light protection technology that can be custom designed to provide complete protection from the solar radiation. Similar technology could enhance the further investigations for deeper understanding of induction, mode of action, and prevention of skin damage from extensive solar irradiation.

Lower Phosphorylation of p38 MAPK Blocks the Oxidative Stress-induced Senescence in Myeloid Leukemic CD34^+CD38^- Cells

Leukemia seems to depend on a small population of ＂leukemia stem cells （LSCs）＂ for its growth and metastasis. However, the precise surviving mechanisms of LSCs remain obscure. Cellular senescence is an important obstacle for production and surviving of tumor cells. In this study we investigated the activated state of a pathway, in which reactive oxygen species （ROS） induces cellular senescence through DNA damage and phophorylation of p38 MAPK （p38）, in myeloid leukemic CD34＋CD38- cells. Bone marrow samples were obtained from patients with acute myeloid leukemia （AML, n=11） and chronic myeloid leukemia （CML, n=9）. CD34＋CD38- cells were isolated from mononuclear cells from these bone marrow samples, and K562 and KG1a cells （two kinds of myeloid leukemia cell lines） by mini-magnetic activated cell sorting. Hematopoietic stem cells （HSCs） from human cord blood served as controls. Intracellular ROS level was detected by flow cytometry. DNA damage defined as the γH2AX level was measured by immunofluorescence staining. Real-time RT-PCR was used to detect the expression of p21, a senescence-associated gene. Western blotting and immunofluo-rescence staining were employed to determine the p38 expression and activation. The proliferation and apoptosis of CD34＋CD38- cells were detected by MTT assay and flow cytometry. Our results showed that ROS and DNA damage were substantially accumulated and p38 was less phosphorated in myeloid leukemic CD34＋CD38- cells as compared with HSCs and H2O2-induced senescent HSCs. Furthermore, over-phosphorylation of p38 by anisomycin, a selective activator of p38, induced both the senescence-like growth arrest and apoptosis of CD34＋CD38- cells from K562 and KG1a cell lines. These findings suggested that, although excessive accumulation of oxidative DNA damage was present in LSCs, the relatively decreased phosphorylation of p38 might help leukemic cells escape senescence and apoptosis.