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Published on: June 16, 2019
Proteomic analysis of different temporal expression patterns induced by N-methyl-N'-nitro-N-nitrosoguanidine
Jing Shen1, Wenzhang Chen, Xuefeng Yin
1Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Abstract:
We have previously shown that N-methyl- N'-nitro- N-nitrosoguanidine (MNNG), a well-known DNA alkylating agent and carcinogen, can induce multiple cellular responses with dynamic characteristics, including such responses as nontargeted mutations (NTM) at undamaged bases in DNA, up-regulation of low fidelity DNA polymerases, clustering of epidermal growth factor receptor (EGFR) and interference with its downstream signaling pathway. A dose-related analysis also revealed that different concentrations of MNNG can trigger diverse proteome changes associated with different cytotoxic effects. To further understand the dynamic cellular responses and hazardous effects caused by environmental carcinogen, a proteomic time-course study of whole cellular proteins from human amniotic epithelial cells after MNNG treatment was performed. Analysis at three different time points (3, 12 and 24 h after exposure) revealed that the major changes were taking place around 3 and 12 h after exposure. Using MALDI-TOF MS coupled with a micro solid-phase extraction (SPE) device, 90% ( n = 70) differentially expressed proteins were identified. Functional assignment revealed that many important pathways were affected, including the protein biosynthesis pathway and Ran GTPase system. We also carried out a network analysis of these proteins and the data suggest a central role for some key regulators in different pathways.
Insights
N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), a carcinogen, triggers dynamic cellular responses and proteome changes. This study reveals key protein pathway alterations and regulators involved in MNNG
Area of Science:
- Proteomics
- Cellular Biology
- Toxicology
Background:
- N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) is a DNA alkylating agent and carcinogen.
- MNNG induces cellular responses including mutations, altered DNA polymerase activity, and EGFR pathway interference.
- Previous studies indicated dose-dependent proteome changes and cytotoxic effects.
Purpose of the Study:
- To investigate the dynamic cellular proteomic responses to MNNG exposure over time.
- To identify key proteins and pathways affected by MNNG in human amniotic epithelial cells.
- To understand the hazardous effects of environmental carcinogens on cellular systems.
Main Methods:
- Proteomic time-course study of human amniotic epithelial cells.
- Treatment with MNNG at various concentrations.
- Analysis at 3, 12, and 24 hours post-exposure.
- Identification of differentially expressed proteins using MALDI-TOF MS and SPE.
- Functional and network analysis of identified proteins.
Main Results:
- Major proteomic changes occurred 3 and 12 hours after MNNG exposure.
- 90% of differentially expressed proteins (70 proteins) were identified.
- Affected pathways include protein biosynthesis and the Ran GTPase system.
- Network analysis suggested central roles for key regulatory proteins.
Conclusions:
- MNNG exposure induces significant dynamic changes in cellular proteomes.
- Protein biosynthesis and Ran GTPase pathways are critical targets of MNNG toxicity.
- Identifying key regulators provides insights into cellular responses to carcinogen exposure.
