Abstract
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is implicated in cell death in addition to a role as a glycolytic enzyme. In particular, when cells are exposed to cellular stressors involving nitric oxide (NO) production, GAPDH can undergo NO-induced S-nitrosylation and S-nitrosylated GAPDH has been shown to elicit apoptosis. However, the mechanism underlying the regulation of the pro-apoptotic function of GAPDH remains unclear. Here, we found that protein arginine methyltransferase 1 (PRMT1) mediated arginine methylation of GAPDH in primary bone marrow-derived macrophages in a NO-dependent manner. Moreover, PRMT1 inhibited S-nitrosylation of GAPDH as well as its binding to SIAH1, thereby reducing the nuclear translocation of GAPDH in lipopolysaccharide (LPS)/interferon (IFN)-γ-activated macrophages. Furthermore, depletion of PRMT1 expression by RNA interference potentiated LPS/IFN-γ-induced apoptosis in macrophages. Taken together, our results suggest that PRMT1 has a previously unrecognized function to inhibit activation-induced cell death of macrophages through arginine methylation of GAPDH.
| Original language | English |
|---|---|
| Journal | Experimental Cell Research |
| DOIs | |
| Publication status | Accepted/In press - 2018 Jan 1 |
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Keywords
- Arginine methylation/GAPDH/ macrophage/nitric oxide/PRMT1
ASJC Scopus subject areas
- Cell Biology
Cite this
PRMT1 negatively regulates activation-induced cell death in macrophages by arginine methylation of GAPDH. / Cho, Jun Ho; Lee, Rana; Kim, Eunju; Choi, Yea Eun; Choi, Eui Ju.
In: Experimental Cell Research, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PRMT1 negatively regulates activation-induced cell death in macrophages by arginine methylation of GAPDH
AU - Cho, Jun Ho
AU - Lee, Rana
AU - Kim, Eunju
AU - Choi, Yea Eun
AU - Choi, Eui Ju
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is implicated in cell death in addition to a role as a glycolytic enzyme. In particular, when cells are exposed to cellular stressors involving nitric oxide (NO) production, GAPDH can undergo NO-induced S-nitrosylation and S-nitrosylated GAPDH has been shown to elicit apoptosis. However, the mechanism underlying the regulation of the pro-apoptotic function of GAPDH remains unclear. Here, we found that protein arginine methyltransferase 1 (PRMT1) mediated arginine methylation of GAPDH in primary bone marrow-derived macrophages in a NO-dependent manner. Moreover, PRMT1 inhibited S-nitrosylation of GAPDH as well as its binding to SIAH1, thereby reducing the nuclear translocation of GAPDH in lipopolysaccharide (LPS)/interferon (IFN)-γ-activated macrophages. Furthermore, depletion of PRMT1 expression by RNA interference potentiated LPS/IFN-γ-induced apoptosis in macrophages. Taken together, our results suggest that PRMT1 has a previously unrecognized function to inhibit activation-induced cell death of macrophages through arginine methylation of GAPDH.
AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is implicated in cell death in addition to a role as a glycolytic enzyme. In particular, when cells are exposed to cellular stressors involving nitric oxide (NO) production, GAPDH can undergo NO-induced S-nitrosylation and S-nitrosylated GAPDH has been shown to elicit apoptosis. However, the mechanism underlying the regulation of the pro-apoptotic function of GAPDH remains unclear. Here, we found that protein arginine methyltransferase 1 (PRMT1) mediated arginine methylation of GAPDH in primary bone marrow-derived macrophages in a NO-dependent manner. Moreover, PRMT1 inhibited S-nitrosylation of GAPDH as well as its binding to SIAH1, thereby reducing the nuclear translocation of GAPDH in lipopolysaccharide (LPS)/interferon (IFN)-γ-activated macrophages. Furthermore, depletion of PRMT1 expression by RNA interference potentiated LPS/IFN-γ-induced apoptosis in macrophages. Taken together, our results suggest that PRMT1 has a previously unrecognized function to inhibit activation-induced cell death of macrophages through arginine methylation of GAPDH.
KW - Arginine methylation/GAPDH/ macrophage/nitric oxide/PRMT1
UR - http://www.scopus.com/inward/record.url?scp=85045877391&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045877391&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2018.04.012
DO - 10.1016/j.yexcr.2018.04.012
M3 - Article
C2 - 29665354
AN - SCOPUS:85045877391
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
ER -