Regulation of tumor suppressor PDCD4 by novel protein kinase C isoforms

AbstractTransforming growth factor-β1 (TGF-β1) induces apoptosis in normal hepatocytes and hepatoma cells. PDCD4 is involved in TGF-β1-induced apoptosis via the Smad pathway. The tumor promoter 12-O-tetradecanoylphorbor-13-acetate (TPA), a protein kinase C stimulator, inhibits TGF-β1-induced apoptosis. However, the mechanisms of TPA action on PDCD4 expression remain to be elucidated. Therefore. the regulatory mechanism of PDCD4 expression by PKC was investigated. The treatment of the human hepatoma cell line, Huh7 with TPA suppressed PDCD4 protein expression and TGF-β1 failed to increase the PDCD4 protein expression. PKC inhibitors Ro-31-8425 or bisindolylmaleimide-1-hydrocholoride (pan-PKC inhibitors) and rottlerin (PKCδ inhibitor), but not Go6976 (PKCα inhibitor), enhanced the induction of PDCD4 protein by TGF-β1. Furthermore, siRNA-mediated knockdown of PKCδ and ε, but not PKCα, augmented the TGF-β1-stimulated PDCD4 protein expression. However, TPA or pan-PKC inhibitor did not alter the PDCD4 mRNA expression either under basal- and TGF-β1-treated conditions. The down-regulation of PDCD4 by TPA was restored by treatment with the proteasome inhibitor MG132. These data suggest that two isoforms of PKCs are involved in the regulation of the PDCD4 protein expression related to the proteasomal degradation pathway

Physiological response of adult Antarctic krill, Euphausia superba, to long-term starvation

Adult Euphausia superba survive winter without or with little feeding. It is not exactly known whether the scarcity of food or an internal clock, set by the natural Antarctic light regime, are responsible for non-feeding. Our research questions were therefore the following: (1) How will physiological and biochemical conditions of krill change during long-term starvation at constant light regime? (2) If and how do enzyme activities change during such starvation? (3) What is the influence of food availability versus that of light regime? To answer these questions, adult krill were starved under laboratory conditions for 12 weeks with constant light regime (12:12; dark/light) and the impact on physiological functions was studied. Initial experimental condition of krill resembled the condition of late spring krill in the field with fully active metabolism and low lipid reserves. Metabolic activity and activities of enzymes catabolising lipids decreased after the onset of starvation and remained low throughout, whereas lipid reserves declined and lipid composition changed. Mass and size of krill decreased while the inter-moult period increased. Depletion of storage- and structural metabolites occurred in the order of depot lipids and glycogen reserves after onset of starvation until proteins were almost exclusively used after 6–7 weeks of starvation. Results confirmed various proposed overwintering mechanisms such as metabolic slowdown, slow growth or shrinkage and use of lipid reserves. However, these changes were set in motion by food shortage only, i.e.without the trigger of a changing light regime

Non-infectious complications of continuous ambulatory peritoneal dialysis and their impact on technique survival

Data on non-infectious complications of continuous ambulatory peritoneal dialysis (CAPD) are sparingly reported from different centres of the country. We studied the non-infectious complications in patients of end stage-renal disease (ESRD) undergoing CAPD. Double-cuffed straight catheter was inserted in all patients using the surgical method and CAPD was started on the 15th day of catheter insertion. The nature of non-infectious complications was noted during follow-up in these patients. Forty-five (male 31, female 14) patients with the mean age of 54.5±11.6 years were studied. Diabetic nephropathy was the most common (59.5%) cause of ESRD. Overall, non-infectious complications were noted in 18/45 (40%) cases. Ultrafiltration failure was the most common (15.5%) followed by incisional hernia (6.6%), exit site leak (4.4%), hydrothorax (4.4%), catheter malposition (4.4%), scrotal swelling (2.2%) and hemoperitoneum (2.2%). Patients with ultrafiltration failure were either shifted to hemodialysis or underwent renal transplantation. The remaining (62%) non-infectious complications did not affect the catheter survival and CAPD could be continued. Non-infectious complications occurred in 40% of our CAPD patients and ultrafiltration failure was the most common (15.5%). A majority (62%) of the complications did not affect catheter survival