Trpc2 depletion protects red blood cells from oxidative stress-induced hemolysis.

Abstract

Transient receptor potential (TRP) channels Trpc2 and Trpc3 are expressed on normal murine erythroid precursors, and erythropoietin stimulates an increase in intracellular calcium ([Ca(2+)](i)) through TRPC2 and TRPC3. Because modulation of [Ca(2+)](i) is an important signaling pathway in erythroid proliferation and differentiation, Trpc2, Trpc3, and Trpc2/Trpc3 double knockout mice were utilized to explore the roles of these channels in erythropoiesis. Trpc2, Trpc3, and Trpc2/Trpc3 double knockout mice were not anemic, and had similar red blood cell counts, hemoglobins, and reticulocyte counts as wild-type littermate controls. Although the erythropoietin-induced increase in [Ca(2+)](i) was reduced, these knockout mice showed no defects in red cell production. The major phenotypic difference at steady state was that the mean corpuscular volume, mean corpuscular hemoglobin, and hematocrit of red cells were significantly greater in Trpc2 and Trpc2/Trpc3 double knockout mice, and mean corpuscular hemoglobin concentration was significantly reduced. All hematological parameters in Trpc3 knockout mice were similar to controls. When exposed to phenylhydrazine, unlike the Trpc3 knockouts, Trpc2 and Trpc2/Trpc3 double knockout mice showed significant resistance to hemolysis. This was associated with a significant reduction in hydrogen peroxide-induced calcium influx in erythroblasts. Although erythropoietin-induced calcium influx through TRPC2 or TRPC3 is not critical for erythroid production, these data demonstrate that TRPC2 plays an important role in oxidative stress-induced hemolysis, which may be related to reduced calcium entry in red cells in the presence of Trpc2 depletion.

• Authors: Iwona Hirschler-Laszkiewicz, Wenyi Zhang, Kerry Keefer, Kathleen Conrad, Qin Tong, Shu-jen Chen, Sarah Bronson, Joseph Y Cheung, Barbara A Miller
• Journal: Experimental hematology (Exp Hematol) Vol. 40 Issue 1 Pg. 71-83 (Jan 2012) ISSN: 1873-2399 [Electronic] Netherlands
• PMID: 21924222 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Chemical References

• Phenylhydrazines
• TRPC Cation Channels
• TRPC3 cation channel
• Trpc2 protein, mouse
• phenylhydrazine

Topics

• Animals
• Erythrocytes (metabolism)
• Hemolysis (drug effects)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Oxidative Stress (drug effects)
• Phenylhydrazines (pharmacology)
• TRPC Cation Channels (deficiency, metabolism)