PMID- 22308457
OWN - NLM
STAT- MEDLINE
DCOM- 20120420
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 7
DP  - 2012 Feb 14
TI  - Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial 
      respiration.
PG  - 2539-43
LID - 10.1073/pnas.1120645109 [doi]
AB  - Platelets are important mediators of blood coagulation that lack nuclei, but 
      contain mitochondria. Although the presence of mitochondria in platelets has long 
      been recognized, platelet mitochondrial function remains largely unaddressed. On 
      the basis of a small amount of literature that suggests platelet mitochondria are 
      functional, we hypothesized that the inhibition of platelet mitochondria disrupts 
      platelet function and platelet-activated blood coagulation. To test this 
      hypothesis, members of the tetrazole, thiazole, and 1,2,3-triazole families of 
      small molecule heterocycles were screened for the ability to inhibit isolated 
      mitochondrial respiration and coagulation of whole blood. The families of 
      heterocycles screened were chosen on the basis of the ability of the heterocycle 
      family to inhibit a biomimetic model of cytochrome c oxidase (CcO). The strength 
      of mitochondrial inhibition correlates with each compound's ability to deter 
      platelet stimulation and platelet-activated blood clotting. These results suggest 
      that for this class of molecules, inhibition of blood coagulation may be 
      occurring through a mechanism involving mitochondrial inhibition.
FAU - Barile, Christopher J
AU  - Barile CJ
AD  - Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
FAU - Herrmann, Paul C
AU  - Herrmann PC
FAU - Tyvoll, David A
AU  - Tyvoll DA
FAU - Collman, James P
AU  - Collman JP
FAU - Decreau, Richard A
AU  - Decreau RA
FAU - Bull, Brian S
AU  - Bull BS
LA  - eng
GR  - R01 GM069658/GM/NIGMS NIH HHS/United States
GR  - GM-069658/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120130
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Biomimetics
MH  - *Blood Coagulation
MH  - Blood Platelets/*metabolism
MH  - Electron Transport Complex IV/metabolism
MH  - Mitochondria/enzymology/*metabolism
MH  - Oxygen/*metabolism
PMC - PMC3289322
COIS- Conflict of interest statement: A patent application has been filed by the 
      authors on the compounds described in this paper.
EDAT- 2012/02/07 06:00
MHDA- 2012/04/21 06:00
PMCR- 2012/08/14
CRDT- 2012/02/07 06:00
PHST- 2012/02/07 06:00 [entrez]
PHST- 2012/02/07 06:00 [pubmed]
PHST- 2012/04/21 06:00 [medline]
PHST- 2012/08/14 00:00 [pmc-release]
AID - 1120645109 [pii]
AID - 201120645 [pii]
AID - 10.1073/pnas.1120645109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2539-43. doi: 
      10.1073/pnas.1120645109. Epub 2012 Jan 30.