Autophagy Ameliorates Reactive Oxygen Species-Induced Platelet Storage Lesions

Abstract

Platelet transfusion is a life-saving therapy to prevent bleeding; however, the availability of platelets for transfusion is limited by the markedly short shelf life owing to the development of platelet storage lesions (PSLs). The mechanism of PSLs remains obscure. Dissection of the intracellular biological changes in stored platelets may help to reduce PSLs and improve platelet transfusion efficiency. In the present study, we explore the changes of stored platelets at room temperature under constant agitation. We found that platelets during storage showed an increased reactive oxygen species (ROS) generation accompanied with receptor shedding, apoptosis, and diminished platelet aggregation. ROS scavenger reduced platelet shedding but also impaired platelet aggregation. Autophagy is a conserved catabolic process that sequesters protein aggregates and damaged organelles into lysosomes for degradation and platelets’ own intact autophagic system. We revealed that there exist a stable autophagic flux in platelets at the early stage of storage, and the autophagic flux in platelets perished after long-term storage. Treatment stored platelets with rapamycin, which stimulates autophagy in eukaryotic cells, markedly ameliorated PSLs, and improved platelet aggregation in response to extracellular stimuli.

In Vitro Transcriptional Response of Eimeria tenella to Toltrazuril Reveals That Oxidative Stress and Autophagy Contribute to Its Anticoccidial Effect

“…This probably indicates that the cell death process begins in the parasite. Previous studies have shown that oxidative stress also leads to the generation of autophagic responses [49][50][51]. Therefore, we speculate that toltrazuril may lead to parasite autophagy by enhancing oxidative stress.…”

Liposomal Resveratrol Alleviates Platelet Storage Lesion via Antioxidation and the Physical Buffering Effect

“…There are some well-defined platelet regulatory factors, for example, NO, prostacyclin (PGI2), adenosine, and ROS, that play roles in platelet activation. For instance, excess ROS generation and oxidative stress during platelet storage are closely related to PSL . ROS can cause activation of the stored platelets through multiple pathways: (1) intraplatelet ROS trigger the activation of αIIbβ3, which causes platelet aggregation upon activation; (2) ROS scavenge NO in platelets, resulting in platelet activation; (3) ROS damage the mitochondrial membrane integrity and compromise the functions of nucleic acids, lipids, and proteins in the platelets, resulting in platelet apoptosis. , Mitochondrial dysfunction affects the normal synthesis of ATP and the bioenergetic state of platelets .…”

“…9,10 ROS are generated by NADPH oxidase, p66Shc oxidase, COX oxidase, and the mitochondrial respiratory chain. 11 Increased ROS levels can lead to platelet apoptosis, 12 activation, 13 loss of platelet adhesiveness and aggregation to reactive matrixes, 14 and a decline in platelet quality. 15 Notably, the concentrated platelets stored in an incubator and agitator undergo deleterious changes due to the physical interaction among the platelets and between them with the environment.…”

“…Factors that initiate PSL include storage duration and temperature, storage medium, container, and mode of agitation. , Both physical and chemical stimuli can affect platelet state, with excessive reactive oxygen species (ROS) accumulation being a primary cause for PSL. , ROS are generated by NADPH oxidase, p66Shc oxidase, COX oxidase, and the mitochondrial respiratory chain . Increased ROS levels can lead to platelet apoptosis, activation, loss of platelet adhesiveness and aggregation to reactive matrixes, and a decline in platelet quality . Notably, the concentrated platelets stored in an incubator and agitator undergo deleterious changes due to the physical interaction among the platelets and between them with the environment …”