Dexamethasone converts pluripotent pancreatic AR42J cells into exocrine cells expressing digestive enzymes. In order to address molecular mechanism of this differentiation, we have investigated the role of mitogen-activated protein (MAP) kinase pathway and gene expressions of p21(waf1/cip1)and nuclear oncogenes (c-fos and c-myc) during AR42J cell differentiation. Dexamethasone markedly increased the intracellular and secreted amylase contents as well as its mRNA level. However, cell growth and DNA content were significantly decreased. With these phenotypic changes, AR42J cells induced transient mRNA expression of p21(waf1/cip1)gene, which reached maximal level by 6 h and then declined gradually toward basal state. In contrast to p21(waf1/cip1), c-fos gene expression was transiently inhibited by 6 h and then recovered to basal level by 24 h. Increased c-myc expression detected after 3 h, peaked by 12 h, and remained elevated during the rest of observation. Dexamethasone inhibited epidermal growth factor-induced phosphorylation of extracellular signal regulated kinase. Inhibition of MAP kinase pathway by PD98059 resulted in further elevation of the dexamethasone-induced amylase mRNA and p21(waf1/cip1)gene expression. These results suggest that p21(waf1/cip1)and nuclear oncogenes are involved in dexamethasone-induced differentiation and inhibition of MAP kinase pathway accelerates the conversion of undifferentiated AR42J cells into amylase-secreting exocrine cells.
Amylases/genetics ; Animals ; Cell Differentiation/*drug effects ; Cell Division/drug effects ; Cell Line, Tumor ; Cyclins/genetics/*metabolism ; Dexamethasone/*pharmacology ; Gene Expression Regulation/drug effects ; Genes, fos/genetics ; Genes, myc/genetics ; MAP Kinase Signaling System/*drug effects ; Mitogen-Activated Protein Kinases/*metabolism ; Pancreas/cytology/*drug effects/enzymology/metabolism ; RNA, Messenger/genetics/metabolism ; Rats ; Support, Non-U.S. Gov't

The reactive oxygen species (ROS) are considered to be an important mediator in pancreatic beta cell destruction, thereby triggering the development of insulin-dependent diabetes mellitus. In the present study, HIV-1 Tat-mediated transduction of Cu, Zn-superoxide dismutase (SOD) was investigated to evaluate its protective potential against streptozotocin (STZ) -induced cytotoxicity in insulin-producing MIN6N cells. Tat-SOD fusion protein was successfully delivered into MIN6N cells in a dose-dependent manner and the transduced fusion protein was enzymatically active for 48 h. The STZ induced-cell destruction, superoxide anion radical production, and DNA fragmentation of MIN6N cells were significantly decreased in the cells pretreated with Tat-SOD for 1 h. Furthermore, the transduction of Tat-SOD increased Bcl-2 and heat shock protein 70 (hsp70) expressions in cells exposed to STZ, which might be partly responsible for the effect of Tat-SOD. These results suggest that an increased of free radical scavenging activity by transduction of Tat-SOD enhanced the tolerance of the cell against oxidative stress in STZ-treated MIN6N cells. Therefore, this Tat-SOD transduction technique may provide a new strategy to protect the pancreatic beta cell destruction in ROS-mediated diabetes.
Diabetes Mellitus, Type 1 ; DNA Fragmentation ; HIV-1 ; HSP70 Heat-Shock Proteins ; Insulin-Secreting Cells ; Oxidative Stress ; Reactive Oxygen Species ; Streptozocin ; Superoxide Dismutase ; Superoxides

PURPOSE: This study was to develop and prove the effects of aself management compliance promotion program for primary hypertension patients who reside in rural communities. METHOD: The content of the self management compliance promotion program developed by this study was as follows: A leader trains patients as a group or individually, in walking, education and green tea therapy from the first to twelfth week. From the thirteenth to twenty fourth week, the patients should perform walking and green tea therapy by themselves. One hundred twenty subjects volunteered to participate in the study, who were among those registered as hypertension patients in the 14 community health clinics located in Chungcheongbuk-do. RESULT: Systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglyceride, step width, and degree of obesity decreased significantly. High-density lipoprotein cholesterol, step length, knowledge of hypertension, and self management compliance significantly increased. CONCLUSION: A self management compliance promotion program for primary hypertensive patients enhances biophysical index and knowledge on hypertension, thus ultimately suggesting a nursing intervention for promoting self management compliance.
Adult ; Aged ; Aged, 80 and over ; Female ; Health Promotion ; Humans ; Hypertension/psychology/*therapy ; Life Style ; Male ; Middle Aged ; Patient Compliance ; *Patient Education as Topic ; Rural Population ; *Self Care