Beyond Protein Synthesis; The Multifaceted Roles of Tuberin in Cell Cycle Regulation.

The ability of cells to sense diverse environmental signals, including nutrient availability and conditions of stress, is critical for both prokaryotes and eukaryotes to mount an appropriate physiological response. While there is a great deal known about the different biochemical pathways that can detect and relay information from the environment, how these signals are integrated to control progression through the cell cycle is still an expanding area of research. Over the past three decades the proteins Tuberin, Hamartin and TBC1D7 have emerged as a large protein complex called the Tuberous Sclerosis Complex. This complex can integrate a wide variety of environmental signals to control a host of cell biology events including protein synthesis, cell cycle, protein transport, cell adhesion, autophagy, and cell growth. Worldwide efforts have revealed many molecular pathways which alter Tuberin post-translationally to convey messages to these important pathways, with most of the focus being on the regulation over protein synthesis. Herein we review the literature supporting that the Tuberous Sclerosis Complex plays a critical role in integrating environmental signals with the core cell cycle machinery.

Glutathione metabolic enzyme activities in diabetic platelets as a function of glycemic control.

Type 1 diabetic subjects categorized on the basis of the glycated haemoglobin content of their blood (low less than 7%; medium, greater than 7% and less than 11%; high, greater than 11%) were analyzed for total intraplatelet GSH as well as for the steady-state kinetic parameters (apparent KM and apparent Vmax) of some glutathione metabolic enzymes including glutathione reductase, glutathione peroxidase, gamma-glutamyltrans-peptidase and glutathione-S-transferase. This study indicates that intraplatelet GSH content of subjects with low glycated-haemoglobin is approximately 2-fold higher than those with medium glycated-haemoglobin. There was no further decrease in intraplatelet-GSH in subjects with high glycated-haemoglobin. The kinetic parameters of the platelet-enzymes studied (glutathione reductase, gamma-glutamyltranspeptidase and glutathione-S-transferase) were essentially independent of the glycation state of the subject. However, the apparent KM of glutathione peroxidase was approximately 4-fold higher in the subjects with high glycated-haemoglobin, in comparison to low subjects. This decrease in affinity could possibly result from the susceptibility of this enzyme to non-enzymatic glucosylation as purified samples of glutathione peroxidase incubated in vitro with glucose showed similar increases in apparent KM. These results are discussed in terms of the potential contribution of glutathione peroxidase impairment, to the hyperaggregability of the diabetic platelet.