Scavenger receptor class BI mediates the anti-apoptotic effect of erythropoietin

Takamasa Nishiuchi1, Koji Murao, Hitomi Imachi

  • 1Division of Endocrinology & Metabolism and Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe Miki-Cho, Kita-gun, Kagawa, 761-0793, Japan.

Annals of Medicine
|February 17, 2010
PubMed

A scavenger receptor of the B class (SR-BI)/human homolog of SR-BI, CD36, and LIMP II analogous-1 (CLA-1), has been identified as a receptor for high-density lipoprotein (HDL). Mice lacking SR-B1 develop anemia, plausibly explained by the observation that the erythrocyte life-span in these animals is reduced. Erythropoietin (EPO) is known to promote survival of erythroid cells, in large part through protection from apoptosis. We have examined the role of EPO on hSR-BI/CLA-1 expression and erythrocyte apoptosis. Endogenous expression of hSR-BI/CLA-1 was increased by exposure to EPO. EPO increased transcriptional activity of hSR-BI/CLA-1 promoter. The stimulatory effect of EPO on hSR-BI/CLA-1 promoter activity was abrogated by LY294002, specific inhibitor of phosphatidylinositol-3 kinase (PI3K). Constitutively active Akt stimulates the activity of the hSR-BI/CLA-1 promoter and a dominant-negative mutant of Akt abolished the ability of EPO to stimulate promoter activity. Finally, EPO in combination with HDL protected the cell from apoptosis, which suggests that hSR-BI/CLA-1 induced by EPO might contribute to the erythrocyte life-span.

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
ER Retrieval Pathway01:45

ER Retrieval Pathway

In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.