High-density lipoprotein protects cardiomyocytes against necrosis induced by oxygen and glucose deprivation through SR-B1, PI3K, and AKT1 and 2
| Autor: | Kevin M. Chathely, Kristina K. Durham, Bernardo L. Trigatti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD36 Antigens medicine.medical_specialty Programmed cell death Necrosis Necroptosis AKT1 cardiomyocytes 030204 cardiovascular system & hematology high-density lipoprotein Biochemistry 03 medical and health sciences Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Internal medicine medicine Animals Humans Myocytes Cardiac Scavenger receptor Phosphorylation Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Research Articles Mice Knockout Chemistry Cell Biology medicine.disease Mice Inbred C57BL Oxygen 030104 developmental biology Endocrinology cell death Glucose lipids (amino acids peptides and proteins) medicine.symptom Lipoproteins HDL Reperfusion injury Proto-Oncogene Proteins c-akt Research Article Signal Transduction |
| Zdroj: | Biochemical Journal |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | The cardioprotective lipoprotein HDL (high-density lipoprotein) prevents myocardial infarction and cardiomyocyte death due to ischemia/reperfusion injury. The scavenger receptor class B, type 1 (SR-B1) is a high-affinity HDL receptor and has been shown to mediate HDL-dependent lipid transport as well as signaling in a variety of different cell types. The contribution of SR-B1 in cardiomyocytes to the protective effects of HDL on cardiomyocyte survival following ischemia has not yet been studied. Here, we use a model of simulated ischemia (oxygen and glucose deprivation, OGD) to assess the mechanistic involvement of SR-B1, PI3K (phosphatidylinositol-3-kinase), and AKT in HDL-mediated protection of cardiomyocytes from cell death. Neonatal mouse cardiomyocytes and immortalized human ventricular cardiomyocytes, subjected to OGD for 4 h, underwent substantial cell death due to necrosis but not necroptosis or apoptosis. Pretreatment of cells with HDL, but not low-density lipoprotein, protected them against OGD-induced necrosis. HDL-mediated protection was lost in cardiomyocytes from SR-B1−/− mice or when SR-B1 was knocked down in human immortalized ventricular cardiomyocytes. HDL treatment induced the phosphorylation of AKT in cardiomyocytes in an SR-B1-dependent manner. Finally, chemical inhibition of PI3K or AKT or silencing of either AKT1 or AKT2 gene expression abolished HDL-mediated protection against OGD-induced necrosis of cardiomyocytes. These results are the first to identify a role of SR-B1 in mediating the protective effects of HDL against necrosis in cardiomyocytes, and to identify AKT activation downstream of SR-B1 in cardiomyocytes. |
| Databáze: | OpenAIRE |
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