Asset Details
Do you wish to reserve the book?
The CaMK Family Differentially Promotes Necroptosis and Mouse Cardiac Graft Injury and Rejection
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
The CaMK Family Differentially Promotes Necroptosis and Mouse Cardiac Graft Injury and Rejection
Do you wish to request the book?
The CaMK Family Differentially Promotes Necroptosis and Mouse Cardiac Graft Injury and Rejection
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
The CaMK Family Differentially Promotes Necroptosis and Mouse Cardiac Graft Injury and Rejection
2024
Overview
Organ transplantation is associated with various forms of programmed cell death which can accelerate transplant injury and rejection. Targeting cell death in donor organs may represent a novel strategy for preventing allograft injury. We have previously demonstrated that necroptosis plays a key role in promoting transplant injury. Recently, we have found that mitochondria function is linked to necroptosis. However, it remains unknown how necroptosis signaling pathways regulate mitochondrial function during necroptosis. In this study, we investigated the receptor-interacting protein kinase 3 (RIPK3) mediated mitochondrial dysfunction and necroptosis. We demonstrate that the calmodulin-dependent protein kinase (CaMK) family members CaMK1, 2, and 4 form a complex with RIPK3 in mouse cardiac endothelial cells, to promote trans-phosphorylation during necroptosis. CaMK1 and 4 directly activated the dynamin-related protein-1 (Drp1), while CaMK2 indirectly activated Drp1 via the phosphoglycerate mutase 5 (PGAM5). The inhibition of CaMKs restored mitochondrial function and effectively prevented endothelial cell death. CaMKs inhibition inhibited activation of CaMKs and Drp1, and cell death and heart tissue injury (n = 6/group, p < 0.01) in a murine model of cardiac transplantation. Importantly, the inhibition of CaMKs greatly prolonged heart graft survival (n = 8/group, p < 0.01). In conclusion, CaMK family members orchestrate cell death in two different pathways and may be potential therapeutic targets in preventing cell death and transplant injury.
Publisher
MDPI AG
Subject
/ Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics
/ Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
/ Calcium-Calmodulin-Dependent Protein Kinases - metabolism
/ Endothelial Cells - metabolism
/ Graft Rejection - metabolism
/ Heart
/ Heart Transplantation - adverse effects
/ Ischemia
/ Kinases
/ Male
/ Mice
/ Phosphoprotein Phosphatases - genetics
/ Phosphoprotein Phosphatases - metabolism
/ Proteins
/ Receptor-Interacting Protein Serine-Threonine Kinases - genetics
/ Receptor-Interacting Protein Serine-Threonine Kinases - metabolism
