6 research outputs found
Accelerated apoptotic death and <i>in vivo</i> turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2
The mitogen- and stress-activated kinase MSK1/2 plays a decisive role in
apoptosis. In analogy to apoptosis of nucleated cells, suicidal erythrocyte
death called eryptosis is characterized by cell shrinkage and cell membrane
scrambling leading to phosphatidylserine (PS) externalization. Here, we
explored whether MSK1/2 participates in the regulation of eryptosis. To this
end, erythrocytes were isolated from mice lacking functional MSK1/2 (msk−/−)
and corresponding wild-type mice (msk+/+). Blood count, hematocrit, hemoglobin
concentration and mean erythrocyte volume were similar in both msk−/− and
msk+/+ mice, but reticulocyte count was significantly increased in msk−/−
mice. Cell membrane PS exposure was similar in untreated msk−/− and msk+/+
erythrocytes, but was enhanced by pathophysiological cell stressors ex vivo
such as hyperosmotic shock or energy depletion to significantly higher levels
in msk−/− erythrocytes than in msk+/+ erythrocytes. Cell shrinkage following
hyperosmotic shock and energy depletion, as well as hemolysis following
decrease of extracellular osmolarity was more pronounced in msk−/−
erythrocytes. The in vivo clearance of autologously-infused CFSE-labeled
erythrocytes from circulating blood was faster in msk−/− mice. The spleens
from msk−/− mice contained a significantly greater number of PS-exposing
erythrocytes than spleens from msk+/+ mice. The present observations point to
accelerated eryptosis and subsequent clearance of erythrocytes leading to
enhanced erythrocyte turnover in MSK1/2-deficient mice
Epstein-Barr virus infection and altered control of apoptotic pathways in posttransplant lymphoproliferative disorders.
Posttransplant lymphoproliferative disorders (PTLD) represent a spectrum of lymphoid diseases complicating the clinical course of transplant recipients. Most PTLD are Epstein-Barr virus (EBV) associated with viral latency type III. Several in vitro studies have revealed an interaction between EBV latency proteins and molecules of the apoptosis pathway. Data on human PTLD regarding an association between Bcl-2 family proteins and EBV are scarce. We analyzed 60 primary PTLD for expression of 8 anti- (Bcl-2, Bcl-XL, and Mcl-1) and proapoptotic proteins (Bak and Bax), the so-called BH3-only proteins (Bad, Bid, Bim, and Puma), as well as the apoptosis effector cleaved PARP by immunohistochemistry. Bim and cleaved PARP were both significantly (p = 0.001 and p = 5.251e-6) downregulated in EBV-positive compared to EBV-negative PTLD [Bim: 6/40 (15%), cleaved PARP: 10/43 (23%), vs. Bim: 13/16 (81%), cleaved PARP: 12/17 (71%)]. Additionally, we observed a tendency toward increased Bcl-2 protein expression (p = 0.24) in EBV-positive PTLD. Hence, we provide evidence of a distinct regulation of Bcl-2 family proteins in EBV-positive versus negative PTLD. The low-expression pattern of the proapoptotic proteins Bim and cleaved PARP together with the high-expression pattern of the antiapoptotic protein Bcl-2 by trend in EBV-positive tumor cells suggests disruption of the apoptotic pathway by EBV in PTLD, promoting survival signals in the host cell