PRMT1 negatively regulates activation-induced cell death in macrophages by arginine methylation of GAPDH

Journal Article · Sun Jul 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.04.012· OSTI ID:23082348

Cho, Jun-Ho; Lee, Rana; Kim, Eunju; Choi, Yea Eun; Choi, Eui-Ju ^[1]

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1. Department of Life Sciences, Korea University, Seoul, 02841 (Korea, Republic of)

Highlights: • PRMT1 mediates arginine methylation of GAPDH. • PRMT1 inhibits S-nitrosylation of GAPDH in LPS/IFN-γ-activated macrophages. • PRMT1 negatively regulates activation-induced cell death of macrophages through arginine methylation of GAPDH. 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.

• OSTI ID: 23082348
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 368; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
ARGININE
BONE MARROW
INTERFERON
LIPOPOLYSACCHARIDES
METHYL TRANSFERASES
OXIDOREDUCTASES