rongly indicates that MSK1 inhibition leads to the attenuated expression of MITF and EDNRB. Although the abrogated expression PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19713189 of MITF PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19712481 and EDNRB may also be attributable to the inhibition of cAMP-dependent PKA by H89, this possibility can be ruled out by the fact that the activation of CREB in UVB-exposed human melanocytes is mediated predominantly via the activation of p38 but not the cyclic AMP/PKA pathway, an indication that H89 treatment could not abrogate the UVB-stimulated expression of MITF and EDNRB via an interruption of the cAMP/ PKA pathway. This is the first report showing that the MSK1 activation is essentially involved in the CREB activation in UVB-exposed human melanocytes and an antioxidant can directly interrupt UVB-induced MSK1 activation, which leads 
to the abrogation of UVB-induced upregulation of melanocyte-specific proteins such as EDNRB. In conclusion, as shown in Fig 9, our findings indicate for the first time that the increased expression of MITF leading to the up-regulation of the melanocyte-specific protein EDNRB in UVB-exposed human melanocytes is mediated via the activation of the p38/MSK1/CREB pathway but not of the ERK/RSK/CREB pathway. The mode of action by PBE demonstrates that the interruption of MSK1 activation is a new target for antioxidants including PBE which can 13 / 17 UVB Stimulates Endothelin B Saracatinib Receptor via a MSK1 Pathway serve as anti-pigmenting agents in UVB-melanosis. This study provides a deep insight into understanding of signaling mechanisms involved in UVB-accentuated expression of melanocytespecific proteins as well as the regulatory role of redox-sensitive MSK1 in the UVB-activated melanogenic signaling pathway in human melanocytes. ~~ ~~ The application of complementary DNA or RNA molecules or their derivatives for the modulation biological functions of specific RNA is referred to as antisense technology. Antisense oligonucleotides are the major class of antisense agents used for sequence-specific RNA knockdown, and they can also be used to modulate RNA synthesis, maturation and transport. Two different mechanisms account for the inhibitory properties of ASOs. The first mechanism is typically mediated by the steric inhibition of translation machinery operating on the targeted RNA. In general, this mechanism is not associated with the destruction of targeted molecules, and, accordingly, it is most effective for coding RNAs if the ASO target site overlaps with or is located upstream of the initiation codon. The second mechanism relies on the ability of ribonuclease H, a ubiquitous group of cellular enzymes, to cleave the RNA part of the heteroduplexes formed between DNA ASOs and targeted RNA. This mechanism results in the degradation of the targeted RNA and is therefore effective regardless of the position of the ASO binding site. The activity of ASOs depends on many factors, including the efficiency of cell entry, the stability of the complex formed with the targeted RNA and the resistance of the ASO to enzymatic degradation. The low potency of standard RNA and DNA ASOs results from their poor uptake and extremely short intracellular and serum half-lives. Sugar moiety and phosphate backbone modifications have been used to increase the resistance of ASOs to degradation. Some of these modifications also increase the binding efficiency of ASOs to their target sequences and/or may be beneficial for cell entry. However, only phosphorothioate-s, boranophosphate-, oxepane-, cyclohexene-, and f
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