TY - JOUR
T1 - Platelet proteome dynamics in hibernating 13-lined ground squirrels
AU - Cooper, Scott
AU - Wilmarth, Phillip A.
AU - Cunliffe, Jennifer M.
AU - Klimek, John
AU - Pang, Jiaqing
AU - Yunga, Samuel Tassi
AU - Minnier, Jessica
AU - Reddy, Ashok
AU - David, Larry
AU - Aslan, Joseph E.
N1 - Funding Information:
This work was supported by NIH National Heart, Lung, and Blood Institute Grants 1R15HL093680 (to S.C.) and R01HL146549 (to J.E.A.). Mass spectrometric analysis was partially supported by NIH National Eye Institute Center Core Grant P30 EY010572 (to L. D.) and National Cancer Institute Core Grant P30 CA069533 (to L. D.) and shared instrument Grant S10OD-012246 (to L.D.).
Publisher Copyright:
© 2021 the American Physiological Society.
PY - 2021/11
Y1 - 2021/11
N2 - Hibernating mammals undergo a dramatic drop in temperature and blood flow during torpor, yet avoid stasis blood clotting through mechanisms that remain unspecified. The effects of hibernation on hemostasis are especially complex, as cold temperatures generally activate platelets, resulting in platelet clearance and cold storage lesions in the context of blood transfusion. With a hibernating body temperature of 4°C–8°C, 13-lined ground squirrels (Ictidomys tridecemlineatus) provide a model to study hemostasis as well as platelet cold storage lesion resistance during hibernation. Here, we quantified and systematically compared proteomes of platelets collected from ground squirrels at summer (active), fall (entrance), and winter (topor) to elucidate how molecular-level changes in platelets may support hemostatic adaptations in torpor. Platelets were isolated from a total of 11 squirrels in June, October, and January. Platelet lysates from each animal were digested with trypsin prior to 11-plex tandem mass tag (TMT) labeling, followed by LC-MS/MS analysis for relative protein quantification. We measured >700 proteins with significant variations in abundance in platelets over the course of entrance, torpor, and activity—including systems of proteins regulating translation, secretion, metabolism, complement, and coagulation cascades. We also noted species-specific differences in levels of hemostatic, secretory, and inflammatory regulators in ground squirrel platelets relative to human platelets. Altogether, we provide the first ever proteomic characterization of platelets from hibernating animals, where systematic changes in metabolic, hemostatic, and other proteins may account for physiological adaptations in torpor and also inform translational effort to improve cold storage of human platelets for transfusion.
AB - Hibernating mammals undergo a dramatic drop in temperature and blood flow during torpor, yet avoid stasis blood clotting through mechanisms that remain unspecified. The effects of hibernation on hemostasis are especially complex, as cold temperatures generally activate platelets, resulting in platelet clearance and cold storage lesions in the context of blood transfusion. With a hibernating body temperature of 4°C–8°C, 13-lined ground squirrels (Ictidomys tridecemlineatus) provide a model to study hemostasis as well as platelet cold storage lesion resistance during hibernation. Here, we quantified and systematically compared proteomes of platelets collected from ground squirrels at summer (active), fall (entrance), and winter (topor) to elucidate how molecular-level changes in platelets may support hemostatic adaptations in torpor. Platelets were isolated from a total of 11 squirrels in June, October, and January. Platelet lysates from each animal were digested with trypsin prior to 11-plex tandem mass tag (TMT) labeling, followed by LC-MS/MS analysis for relative protein quantification. We measured >700 proteins with significant variations in abundance in platelets over the course of entrance, torpor, and activity—including systems of proteins regulating translation, secretion, metabolism, complement, and coagulation cascades. We also noted species-specific differences in levels of hemostatic, secretory, and inflammatory regulators in ground squirrel platelets relative to human platelets. Altogether, we provide the first ever proteomic characterization of platelets from hibernating animals, where systematic changes in metabolic, hemostatic, and other proteins may account for physiological adaptations in torpor and also inform translational effort to improve cold storage of human platelets for transfusion.
KW - Hypothermia
KW - Lipoprotein
KW - Platelet storage
KW - Proteomics
KW - Transfusion
UR - http://www.scopus.com/inward/record.url?scp=85119699594&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85119699594&partnerID=8YFLogxK
U2 - 10.1152/physiolgenomics.00078.2021
DO - 10.1152/physiolgenomics.00078.2021
M3 - Article
C2 - 34677084
AN - SCOPUS:85119699594
SN - 1094-8341
VL - 53
SP - 473
EP - 485
JO - Physiological Genomics
JF - Physiological Genomics
IS - 11
ER -