Exogenous serum factors

Egelrud, T. and Olivecrona, T. 1973. Purified bovine milk (lipoprotein) lipase Activity against lipid substrates in the absence of exogenous serum factors. Biochem. Bio-phys. Acta 306, 115-127. 

In the absence of anti-differentiation factors such as LIF, mESCs spontaneously differentiate. Early specification of ESCs proceeds similarly to gastrulation, with the commitment of either neuroectoderm or a PS-like population. Neuroectoderm specification is often referred to as the default pathway, because ESCs differentiate into neural precursors with high fidelity without the supplementation of serum of other exogenous growth factors (Ying et al. 2003). Cells have been induced to enter the PS lineage by... 

Transfection ofmouse SlPphosphatase into HEK 293 cells, resulting in a 3-fold increase in membrane SIP phosphatase activity, caused a 50% deaease in SIP levels (reduced by 0.6 pmol/nmol phospholipid) and a 2 fold inaease in ceramide (inaeased by 23 pmol/nmol phospholipid) whereas sphingosine levels were similar to vector controls (0.8 pnnol/nmol phosphohpid). SIP phosphatase transfected cells underwent apoptosis in response to serum withdrawal, C2-ceramide, peroxide or doxorubicin with 2-3 fold higher frequency compared to vector-transfected control cells. Surprisingly, exogenously added SIP, which normally confers protechon, inaeased apoptosis. This may be due to its metabolism to ceramide (Mandala et al, 2000) although other factors may also be involved. 

Age and familial factors in both men and women influence both plasma adrenal androgens (DHEA and DHEA-S). Adrenal androgen secretion starts to rise about the age of 9, peaks at about age 25, and declines after age 30. In the seventh decade of fife, the adrenal androgen concentrations fall to prepubertal concentrations. Thus in the elderly, the circadian variation in plasma DHEA is relatively blunted and dissociated from the circadian variation in cortisol. The adrenal contribution of serum androstenedione declines with age. DHEA and DHEA-S responses to stimulation with exogenous ACTH are... 

The extrinsic pathway is activated by tissue injury and is not of major concern in the clinical use of membrane devices. The intrinsic pathway, however, is initiated by a multitude of factors. Including interactions between serum proteins and exogenous materials. Hydrodynamic forces acting on platelets may also lead to the release of platelet factors that trigger the intrinsic pathway. Thus, the selection of membrane materials to minimize thrombogenesls cannot be fully separated from the design of devices to contain them because of this potential for shear forces to activate the clotting cascade. 

One downstream effector for ceramide-induced apoptosis may be the retinoblastoma protein (Rb). Serum withdrawal induced cell cycle arrest and dephosphorylation of Rb in MOLT-4 cells associated with increased levels of endogenous cera-mide, whereas sphingosine levels were unaffected. Addition of exogenous ceramide also induced dephosphorylation of Rb in these cells. Ceramide did not induce cell cycle arrest in cells that had defective or inactive Rb (Dbaibo et al., 1995). These data are consistent with the current models of Rb action, in which hypophosphorylation of Rb protein correlates with its ability to bind to transcription factors such as those of of the E2F family and to repress progression through the G1 phase of the cell cycle (Ewen, 1994). 

The level of serum cholesterol concentration of any given individual at a certain time obviously depends on a number of factors. Some exogenous influences on serum cholesterol are well recognized as e.g. age, sex, body weight, diet etc. 

The transfer of plasma proteins to tumor tissues was studied by Babson and Winnick (343) who noted that plasma proteins were more efficiently transferred to tumor tissue (Walker carcinoma) than to normal tissue, and were there utilized in preference to free injected amino acid. However, since, as we have seen, exchange of exogenous amino acids with the intracellular pools is not very efficient anyway, such experiments are not meaningful unless the specific activity of the pool amino acids is determined. Moreover, it must be demonstrated that transfer of whole plasma protein does not occur. When all of these factors were taken into consideration, and the amount of intact serum albumin in the different organs determined by immunological means, Campbell and Stone (346) found no evidence for a utilization of breakdown products other than free amino acids. 

---