Annexin A5 as a New Potential Biomarker for Cisplatin-Induced Toxicity in Human Kidney Epithelial Cells

Cisplatin is a member of platinum-containing anti-cancer drugs that causes cross-linking of DNA and ultimately cancer cell apoptosis. The therapeutic function of cisplatin on various types of cancers has been widely reported but the side effects have been discovered together and nephrotoxicity has been regarded as major side effect of cisplatin. To select candidates for new sensitive nephrotoxicity biomarker, we performed proteomic analysis using 2-DE/MALDI-TOF-MS followed by cisplatin treatment in human kidney cell line, HK-2 cells, and compared the results to the gene profi le from microarray composed of genes changed in expression by cisplatin from formerly reported article. Annexin A5 has been selected to be the most potential candidate and it has been identifi ed using Western blot, RT-PCR and cell viability assay whether annexin A5 is available to be a sensitive nephrotoxic biomarker. Treatment with cisplatin on HK-2 cells caused the increase of annexin A5 expression in protein and mRNA levels. Overexpression of annexin A5 blocked HK-2 cell proliferation, indicating correlation between annexin A5 and renal cell toxicity. Taken together, these results suggest the possibility of annexin A5 as a new biomarker for cisplatin-mediated nephrotoxicity.

Induction of steroid sulfatase expression by tumor necrosis factor-alpha through phosphatidylinositol 3-kinase/Akt signaling pathway in PC-3 human prostate cancer cells

Steroid sulfatase (STS) is responsible for the hydrolysis of aryl and alkyl steroid sulfates and has a pivotal role in regulating the formation of biologically active estrogens. STS may be considered a new promising drug target for treating estrogen-mediated carcinogenesis. However, the molecular mechanism of STS expression is not well-known. To investigate whether tumor necrosis factor (TNF)-alpha is able to regulate gene transcription of STS, we studied the effect of TNF-alpha on STS expression in PC-3 human prostate cancer cells. RT-PCR and Western blot analysis showed that TNF-alpha significantly induced the expression of STS mRNA and protein in a concentration- and time-dependent manner. Treatment with TNF-alpha resulted in a strong increase in the phosphorylation of Akt on Ser-473 and when cells were treated with phosphatidylinositol (PI) 3-kinase inhibitors such as LY294002 or wortmannin, or Akt inhibitor (Akt inhibitor IV), induction of STS mRNA expression by TNF-alpha was significantly prevented. Moreover, activation of Akt1 by expressing the constitutively active form of Akt1 increased STS expression whereas dominant-negative Akt suppressed TNF-alpha-mediated STS induction. We also found that TNF-alpha is able to increase STS mRNA expression in other human cancer cells such as LNCaP, MDA-MB-231, and MCF-7 as well as PC-3 cells. Taken together, our results strongly suggest that PI 3-kinase/Akt activation mediates induction of human STS gene expression by TNF-alpha in human cancer cells.

A Comparative Study of Mental Health between the Laid-Off and the Employed Worker in the Similar Industry / 대한산업의학회지

OBJECTIVES: This study was conducted to examine the mental health status of the laid off by comparing the unemployed with the employed. METHODS: A survey questionnaire was used to investigate the mental health status of the laidoff in comparison with that of the employed. The study sample consisted of 247 laid-off people formerly employed in A auto factory and 167 employees working in B auto factory. RESULTS: The proportion exercising regularly was 20.2% for the laid-off and 34.8% for the employed and the proportion having regular meals was 10.9% and 50.6%, respectively. In addition, the frequency and amount of alcohol consumption and smoking of the laid-off were higher than those of the employed. Among the laid-off, 69.4% responded that they spent less time in talking to their spouse, and 65.4% also reported reduced sexual activities with their spouse. Because of unemployment, 41.8% of the laid-off experienced conflicts with their children, and 53.5% also perceived that they were stigmatized and treated badly by their neighbors, friends and relatives. Mean IFR in the laid-off was 22.9, which was much higher than the 15.3 recorded in the employed. The mean PWI-SF was 24.2 for the laid-off and 13.0 for the employed, which indicates the lower psychological health status of the laid-off than that of the employed. Age, annual salary, family relationship, regular exercise, regular diets, possibility to return to work and perception of the future were related to mental health status for the laid-off. Stepwise multiple regression analysis showed that the most important factor influencing mental health status for the laid-off was family relationships. CONCLUSIONS: According to the above results, the mental health of the laid-off is worse than that of the employed. Based on this study, a follow-up study focusing on the mental health status of the reemployed to the same factory, is needed to understand the direct mental health effect on the laid-off.