Adapter molecule DOC-2 is differentially expressed in pressure and volume overload hypertrophy and inhibits collagen synthesis in cardiac fibroblasts.

DOC-2 (differentially expressed in ovarian carcinoma) is involved in Ras-, beta-integrin-, PKC-, and transforming growth factor-beta-mediated cell signaling. These pathways are implicated in the accumulation of extracellular matrix proteins during progression of hypertrophy to heart failure; however, the role of DOC-2 in cardiac pathophysiology has never been examined. This study was undertaken to 1) analyze DOC-2 expression in primary cultures of cardiac fibroblasts and cardiac myocytes and in the heart following different types of hemodynamic overloads and 2) examine its role in growth factor-mediated ERK activation and collagen production. Pressure overload and volume overload were induced for 10 wk in Sprague-Dawley rats by aortic constriction and by aortocaval shunt, respectively. ANG II (0.3 mg.kg(-1).day(-1)) was infused for 2 wk. Results showed that, compared with myocytes, DOC-2 was found abundantly expressed in cardiac fibroblasts. Treatment of cardiac fibroblasts with ANG II and TPA resulted in increased expression of DOC-2. Overexpression of DOC-2 in cardiac fibroblasts led to inhibition of hypertrophy agonist-stimulated ERK activation and collagen expression. An inverse correlation between collagen and DOC-2 was observed in in vivo models of cardiac hypertrophy; in pressure overload and after ANG II infusion, increased collagen mRNA correlated with reduced DOC-2 levels, whereas in volume overload increased DOC-2 levels were accompanied by unchanged collagen mRNA. These data for the first time describe expression of DOC-2 in the heart and demonstrate its modulation by growth-promoting agents in cultured cardiac fibroblasts and in in vivo models of heart hypertrophy. Results suggest a role of DOC-2 in cardiac remodeling involving collagen expression during chronic hemodynamic overload.     

Effect of biomass concentration on the specific solvent productivity ofClostridium acetobutylicum in chemostat culture

Summary Using a defined medium in chemostat culture, an inverse relationship between the biomass concentration and the specific butanol productivity has been observed. It is suggested that this is due to the cell population not being homogeneous, and that a change in the nutrient balance leads to a cha in the relative proportions of acidogenic, solventogenic and inert cells (spores).     

Effect of phosphate and ammonium ion concentrations on solvent production in defined medium byClostridium acetobutylicum

Summary Experiments have been performed in batch fermentation, using a defined medium, to investigate the effects of phosphate and ammonium ion concentrations on solvent production usingClostridium acetobutylicum. Solvent production occurred under conditions of either ammonium- or phosphate-limitation, but the optimum conditions were observed to be where both of these nutrients were slightly in excess of growth requirements. A greater excess of nutrients caused the fermentation to be acidogenic rather than solventogenic.