Microvascular Transport Factors in the Design of Effective Blood Substitutes

Author(s):  
M. Intaglietta
2008 ◽  
Vol 44 ◽  
pp. 63-84 ◽  
Author(s):  
Chris E. Cooper

Optimum performance in aerobic sports performance requires an efficient delivery to, and consumption of, oxygen by the exercising muscle. It is probable that maximal oxygen uptake in the athlete is multifactorial, being shared between cardiac output, blood oxygen content, muscle blood flow, oxygen diffusion from the blood to the cell and mitochondrial content. Of these, raising the blood oxygen content by raising the haematocrit is the simplest acute method to increase oxygen delivery and improve sport performance. Legal means of raising haematocrit include altitude training and hypoxic tents. Illegal means include blood doping and the administration of EPO (erythropoietin). The ability to make EPO by genetic means has resulted in an increase in its availability and use, although it is probable that recent testing methods may have had some impact. Less widely used illegal methods include the use of artificial blood oxygen carriers (the so-called ‘blood substitutes’). In principle these molecules could enhance aerobic sports performance; however, they would be readily detectable in urine and blood tests. An alternative to increasing the blood oxygen content is to increase the amount of oxygen that haemoglobin can deliver. It is possible to do this by using compounds that right-shift the haemoglobin dissociation curve (e.g. RSR13). There is a compromise between improving oxygen delivery at the muscle and losing oxygen uptake at the lung and it is unclear whether these reagents would enhance the performance of elite athletes. However, given the proven success of blood doping and EPO, attempts to manipulate these pathways are likely to lead to an ongoing battle between the athlete and the drug testers.


2005 ◽  
Vol 16 (7) ◽  
pp. 3200-3210 ◽  
Author(s):  
Jennifer L. Hodges ◽  
Jennifer H. Leslie ◽  
Nima Mosammaparast ◽  
Yurong Guo ◽  
Jeffrey Shabanowitz ◽  
...  

Nuclear import and export is mediated by an evolutionarily conserved family of soluble transport factors, the karyopherins (referred to as importins and exportins). The yeast karyopherin Kap114p has previously been shown to import histones H2A and H2B, Nap1p, and a component of the preinitiation complex (PIC), TBP. Using a proteomic approach, we have identified several potentially new cargoes for Kap114p. These cargoes include another PIC component, the general transcription factor IIB or Sua7p, which interacted directly with Kap114p. Consistent with its role as a Sua7p import factor, deletion of KAP114 led to specific mislocalization of Sua7p to the cytoplasm. An interaction between Sua7p and TBP was also detected in cytosol, raising the possibility that both Sua7p and TBP can be coimported by Kap114p. We have also shown that Kap114p possesses multiple overlapping binding sites for its partners, Sua7p, Nap1p, and H2A and H2B, as well as RanGTP and nucleoporins. In addition, we have assembled an in vitro complex containing Sua7p, Nap1p, and histones H2A and H2B, suggesting that this Kap may import several proteins simultaneously. The import of more than one cargo at a time would increase the efficiency of each import cycle and may allow the regulation of coimported cargoes.


Nature ◽  
1992 ◽  
Vol 358 (6381) ◽  
pp. 23-24 ◽  
Author(s):  
B. R. Otto ◽  
A. M. J. J. Verweij-van Vught ◽  
D. M. MacLaren
Keyword(s):  

2011 ◽  
pp. 67-73
Author(s):  
David C. Griffin ◽  
Raminder Nirula
Keyword(s):  

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