What question did this study set out to answer?

To determine whether platelet metalloproteinases mediate the proteolytic shedding and functional down-regulation of glycoprotein VI (GPVI).

January 1, 2004Thrombosis and Haemostasis

GPVI down-regulation in murine platelets through metalloproteinase-dependent shedding

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Authors

ASAmrei StrehlUniversity of Würzburg CPCrystal L. PiffathAdimab (United States)MPMiroslava ProstrednáUniversity of Cologne

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Implication

Experimental study reveals metalloproteinase-dependent shedding of GPVI following mitochondrial injury in mouse platelets, suggesting receptor-specific shedding mechanisms.

Key Points

To determine whether platelet metalloproteinases mediate the proteolytic shedding and functional down-regulation of glycoprotein VI (GPVI).
Induced mitochondrial injury in mouse platelets using carbonyl cyanide m-chlorophenyl-hydrazone (CCCP).
Measured platelet activation responses to collagen, collagen-related peptide (CRP), thrombin, and U46619 in the presence or absence of the broad-spectrum metalloproteinase inhibitor GM6001.
Analyzed the proteolytic cleavage and release of the 55 kDa extracellular domain of GPVI into the supernatant.
Mitochondrial damage prompted rapid proteolytic cleavage of GPVI, releasing a 55 kDa extracellular fragment and selectively impairing activation by collagen and CRP.
Inhibition with GM6001 prevented GPVI proteolysis and preserved GPVI-mediated platelet activation.
Activation by thrombin or CRP stimulated metalloproteinase-dependent shedding of GPIbα but not GPVI, indicating distinct regulatory enzymes or activation triggers for each receptor.

Cite This Study

Strehl et al. (2004) studied this question.

synapsesocial.com/papers/6a6fbe6c3ce530166bc2ae3a https://doi.org/10.1160/th03-12-0795

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Implication

Experimental study reveals metalloproteinase-dependent shedding of GPVI following mitochondrial injury in mouse platelets, suggesting receptor-specific shedding mechanisms.

GPVI down-regulation in murine platelets through metalloproteinase-dependent shedding

Discussion

Member takes

Implication

Key Points

Cite This Study

GPVI down-regulation in murine platelets through metalloproteinase-dependent shedding

Discussion

Member takes

Implication

Key Points

Cite This Study

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