Physiological function of the cellular prion protein (PrPc_1hnc): protein profiling study in two cell culture systems

Front Cover
Logos Verlag Berlin GmbH, Nov 15, 2008 - 134 pages
The physiological role of the cellular prion protein (PrPc) is still not fully understood. This study gives a further insight into the possible physiological function(s) of PrPc via recognizing proteome changes influenced by different levels of PrPc expression in human embryonic kidney (HEK) 293 and PrPc-deficient (Prnp0/0 ) ell line. The two cell lines gave largely non-intersecting results. A high proportion of proteins deregulated following PrPc overexpression in HEK 293 cells is involved in energy metabolism and cellular homeostasis. Hence, the previously reported increased sensitivity of PrPc overexpressing cells to apoptotic stimuli might be caused by perturbed expression of proteins essential for energy production and maintenance of cellular homeostasis. A particularly significant point of the present study is PrPc overexpression-induced regulation of several proteins which are known to contribute to Alzheimer and Parkinson disease pathogenesis. This finding may be helpful in understanding the common molecular mechanisms underlying the pathogenesis of prion diseases and other neurodegenerative disorders. Conversely, the introduction of the human prion protein gene (PRNP) into Prnp0/0 cells correlated positively with regulation of proteins mainly implied in protection against oxidative stress and apoptosis. This finding is in line with earlier reports demonstrating rescue of Prnp0/0 neurons from apoptosis following an introduction of prion protein gene. Altogether, the presence/absence and the level of PrPc expression seem to be crucial for the fluctuation between PrPc's pro- and anti- apoptotic properties. In addition, this study provides first time evidence for PrPc-induced up-regulation of the glycolytic enzyme, lactate dehydrogenase (LDH) after transient focal cerebral ischemia in wild-type mice as compared to Prnp00 mice. The possibility that LDH and its product lactate, known to protect neural tissue against hypoxia/ischemia, might be involved in previously described PrPc-mediated neuroprotection against ischemic injury is considered.
 

What people are saying - Write a review

We haven't found any reviews in the usual places.

Contents

II
1
III
18
IV
25
V
50
VI
78
VII
92
VIII
93
IX
99
Copyright

Common terms and phrases

Bibliographic information