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is known as an adipocyte-specific secretory hormone that can cause insulin resistance and decrease adipocyte differentiation. By contrast, green tea catechins, especially (Ϫ)-epigallocatechin gallate (EGCG), have been reported as body weight and diabetes chemopreventatives. Whether EGCG regulates production of Rstn is unknown. Using 3T3-L1 adipocytes, we found that EGCG at 20 and 100 M suppressed Rstn mRNA levels by ϳ35 and 50%, respectively, after 3 h. The basal half-life of Rstn mRNA induced by actinomycin D was Ͼ12 h but shifted to 3 h in the presence of EGCG. This suggests that EGCG regulates the stability of Rstn mRNA. Treatment with cycloheximide did not prevent EGCGsuppressed Rstn mRNA levels, which suggests that the effect of EGCG does not require new protein synthesis. Intracellular Rstn protein significantly decreased in the presence of 100 M EGCG 3 h after treatment, whereas the release of the Rstn protein did not significantly change. This suggests that EGCG may modulate the distribution of Rstn protein between the intracellular and extracellular compartments. EGCG did not affect the amounts of extracellular signal-related kinase-1/2 (ERK1/2), phospho-JNK, phospho-p38, and phospho-Akt proteins but reduced the amounts of phospho-ERK1/2 proteins. Overexpression with MEK1 blocked EGCG-inhibited Rstn mRNA expression. These data suggest that EGCG downregulates Rstn expression via a pathway that is dependent on the ERK pathway.genistein; mitogen-activated protein kinase; extracellular signal-related kinase RESISTIN (RSTN) IS A CYSTEINE-RICH POLYPEPTIDE HORMONE (20,38) that, depending on the species, contains 4 -5 exons, 3-4 introns, 575-1217 bp of mRNA, and 108 -114 amino acids of protein (10 -12.5 kDa) (16,23,44,45). Rstn is first isolated from adipose tissues and found to link obesity to type 2 diabetes (44). In particular, Rstn mRNA expression in adipose tissues of obese humans is higher than that in normal subjects (12). In addition, a single nucleotide polymorphism in the Rstn gene promoter is associated with obesity (14) and diabetes (35), and the plasma Rstn levels are elevated in patients with obesity (12) and type 2 diabetes (59). Moreover, the dominant negative form of Rstn enhances adipogenesis and improves insulin sensitivity (24). Ever since its discovery, Rstn also has been found to possess numerous other actions. For example, Rstn regulates fasted blood glucose (6), causes dyslipidemia (39), suppresses insulin-stimulated glucose uptake in adipocytes (44) and muscle cells (30), inhibits dopamine and norepinephrine release in the hypothalamus (8), and promotes endothelial cell activation (50) and smooth muscle proliferation (9). To our knowledge, the expression of Rstn gene can be regulated by nutritional, endocrine, genetic, pharmacological, and developmental factors (5), and the mechanisms of action of Rstn are emerging. For example, Rstn promotes smooth muscle cell proliferation through the activation of extracellular signalregulated kinase (ERK1/2) and phosphatidylinositol 3-kinase (PI3K) ...

The results of this study suggest that EGCG mediates anti-IGF-I and anti-IGF-II signals in preadipocyte mitogenesis via the 67LR but not the AMPK pathway.

This study clearly demonstrates that the combined technology of SELDI-TOF MS and artificial intelligence is effective in distinguishing protein expression between normal and ovarian cancer plasma. The identified protein peaks may be candidate proteins for early detection of ovarian cancer or evaluation of therapeutic response.