Toxicology at Environmentally Relevant Concentrations in Caenorhabditis elegans

Preface
Contents
Chapter 1: Toxicity Induction of Toxicants at Environmentally Relevant Concentrations
	1.1 Introduction
	1.2 Toxicity Induction by Long-Term Exposure to Toxicants at ERCs
		1.2.1 Toxicity of Toxicants at ERCs After Chronic Exposure
			1.2.1.1 Chronic Exposure from Adult Day-1 to Day-8
			1.2.1.2 Chronic Exposure from Adult Day-1 to Day-10
			1.2.1.3 Chronic Exposure from L1-Larvae to Adult Day-8
		1.2.2 Toxicity of Toxicants at ERCs After Prolonged Exposure
			1.2.2.1 Prolonged Exposure from L1-Larvae to Adult Day-1
			1.2.2.2 Prolonged Exposure from L1-Larvae to Adult Day-3
	1.3 Toxicity Induction of Toxicants at ERCs Under Oxidative Stress Condition
	1.4 Toxicity Induction of Toxicants at ERCs Under Environmental Stress Condition
		1.4.1 Toxicity Induction of Toxicants at ERCs Under Heat Stress Condition
		1.4.2 Toxicity Induction of Toxicants at ERCs Under Simulated Microgravity Stress Condition
	1.5 Toxicity Induction of Toxicants at ERCs During the Aging Process
	1.6 Toxicity Induction of Toxicants at ERCs Under Susceptible Genetic Backgrounds
	1.7 Toxicity Induction of Toxicants at ERCs in Nematodes with Deficit in Intestinal Barrier
	1.8 Toxicity Induction of Toxicants with Certain Surface Modifications at ERCs
	1.9 Toxicity Induced by Combinational or Sequential Exposure to Toxicants at ERCs
		1.9.1 Toxicity Induced by Combinational Exposure to Toxicants at ERCs
		1.9.2 Toxicity Induced by Sequential Exposure to Toxicants at ERCs
	1.10 Cellular Basis for the Toxicity Induction of Toxicants at ERCs
		1.10.1 Activation of Oxidative Stress
		1.10.2 Enhancement in Intestinal Permeability
		1.10.3 Suppression in Innate Immune Response
		1.10.4 Suppression in Mitochondrial Unfolded Protein Response (mt UPR)
		1.10.5 Prolonged Defecation Cycle Length
	1.11 Perspectives
	References
Chapter 2: Response of Oxidative Stress-Related Molecular Signals to Toxicants at Environmentally Relevant Concentrations
	2.1 Introduction
	2.2 Alteration in Molecular Basis for Oxidative Stress Induced by Toxicants at ERCs
		2.2.1 Alteration in Molecular Basis for Oxidative Stress Induced by Toxicants After Long-Term Exposure
		2.2.2 Alteration in Molecular Basis for Oxidative Stress Induced by Toxicants in Nematodes with Deficit in Intestinal Barrier
		2.2.3 Alteration in Molecular Basis for Oxidative Stress Induced by Combinational Exposure to Different Toxicants
	2.3 Oxidative Stress-Related Molecular Signals Regulating the Response to Toxicants at ERCs
		2.3.1 SOD-2 and SOD-3
		2.3.2 GST-5
		2.3.3 CLK-1 and ISP-1
	2.4 Perspectives
	References
Chapter 3: Response of Insulin Signaling Pathway to Toxicants at Environmentally Relevant Concentrations
	3.1 Introduction
	3.2 Alteration in Expression of Genes Encoding Insulin Signaling Pathway Induced by Toxicants at ERCs
	3.3 Function of Insulin Signaling Pathway in Regulating the Toxicity of Toxicants at ERCs
	3.4 Tissue-Specific Activity of DAF-16 in Regulating the Toxicity of Toxicants at ERCs
	3.5 Identification of Downstream Targets of DAF-16 in Regulating the Toxicity of Toxicants at ERCs
		3.5.1 SOD-3, MTL-1, and GPB-2
		3.5.2 LGG-1
	3.6 Insulin Peptides Involved in Regulating the Toxicity of Toxicants at ERCs
	3.7 Perspectives
	References
Chapter 4: Response of MAPK Signaling Pathways to Toxicants at Environmentally Relevant Concentrations
	4.1 Introduction
	4.2 Response of p38 MAPK Signaling Pathway to Toxicants at ERCs
		4.2.1 Alteration in Expression of Genes Encoding p38 MAPK Signaling Pathway Induced by Toxicants at ERCs
		4.2.2 Functional Analysis of p38 MAPK in Regulating the Response to Toxicants at ERCs
		4.2.3 Tissue-Specific Activity of PMK-1 in Regulating the Response to Toxicants at ERCs
		4.2.4 Identification of Downstream Targets of PMK-1 in Regulating the Response to Toxicants at ERCs
			4.2.4.1 SKN-1 and ATF-7
			4.2.4.2 ATF-7-Mediated Signaling Cascade
			4.2.4.3 SKN-1-Mediated Signaling Cascade
			4.2.4.4 MDT-15 and SBP-1
			4.2.4.5 NHR-8
	4.3 Response of JNK MAPK Signaling Pathway to Toxicants at ERCs
		4.3.1 Alteration in Expression of Genes Encoding JNK MAPK Signaling Pathway Induced by Toxicants at ERCs
		4.3.2 Functional Analysis of JNK MAPK Signaling Pathway in Regulating the Response to Toxicants at ERCs
		4.3.3 Identification of Downstream Targets for JNK-1 in Regulating the Response to Toxicants at ERCs
	4.4 Response of ERK MAPK Signaling Pathways to Toxicants at ERCs
		4.4.1 Alteration in Expression of Genes Encoding ERK MAPK Signaling Pathway Induced by Toxicants at ERCs
		4.4.2 Functional Analysis of ERK MAPK Signaling Pathway in Regulating the Response to Toxicants at ERCs
		4.4.3 Tissue-Specific Activity of MPK-1/ERK MAPK in Regulating the Response to Toxicants at ERCs
		4.4.4 Identification of Downstream Targets of Neuronal MPK-1 in Regulating the Response to Toxicants at ERCs
	4.5 Genetic Interaction Between p38 MAPK Signaling Pathway and Insulin Signaling Pathway in Regulating the Toxicity of Toxican...
	4.6 Perspectives
	References
Chapter 5: Response of Development-Related Signaling Pathways to Toxicants at Environmentally Relevant Concentrations
	5.1 Introduction
	5.2 Response of Intestinal Development-Related Molecular Signals to Toxicants at ERCs
		5.2.1 Alteration in Expression of Intestinal Development-Related Genes Induced by Toxicants at ERCs
		5.2.2 ELT-2 Signal
			5.2.2.1 Alteration in ELT-2 Expression Induced by Toxicants at ERCs
			5.2.2.2 Functional Analysis of ELT-2 in Regulating the Response to Toxicants at ERCs
			5.2.2.3 Tissue-Specific Activity of ELT-2 in Regulating the Response to Toxicants at ERCs
			5.2.2.4 Identification of Downstream Targets of Intestinal ELT-2 in Regulating the Response to Toxicants at ERCs
		5.2.3 ACS-22 Signal
		5.2.4 IFC-2 Signal
	5.3 Response of Cell Death and DNA Damage-Related Signaling Pathways to Toxicants at ERCs
	5.4 Response of Wnt Signaling Pathway to Toxicants at ERCs
		5.4.1 Alteration in Expression of Genes Encoding Wnt Signaling Pathway Induced by Toxicants at ERCs
		5.4.2 Functional Analysis of BAR-1 and GSK-3 in Regulating the Response to Toxicants at ERCs
		5.4.3 Tissue-Specific Activity of BAR-1 in Regulating the Response to Toxicants at ERCs
		5.4.4 Identification of Downstream Targets of Intestinal BAR-1 in Regulating the Response to Toxicants at ERCs
			5.4.4.1 POP-1, DAF-16, and PRX-5
			5.4.4.2 PRX-5-Mediated Signaling Cascade
	5.5 Response of DBL-1-Mediated TGF-β Signaling Pathway to Toxicants at ERCs
		5.5.1 Alteration in Expression of DBL-1 Induced by Toxicants at ERCs
		5.5.2 Tissue-Specific Activity of DBL-1 in Regulating the Response to Toxicants at ERCs
		5.5.3 Identification of Upregulators of DBL-1 in Regulating the Response to Toxicants at ERCs
		5.5.4 Identification of TGF-β Receptors in Regulating the Response to Toxicants at ERCs
		5.5.5 Identification of Cytoplasmic Smads in Regulating the Response to Toxicants at ERCs
		5.5.6 Identification of Transcriptional Factors in Regulating the Response to Toxicants at ERCs
		5.5.7 Identification of Downstream Targets of Intestinal SMA-9 and MAB-31 in Regulating the Response to Toxicants at ERCs
	5.6 Response of DAF-7-Mediated TGF-β Signaling Pathway to Toxicants
		5.6.1 Role of DAF-7 in Regulating the Response to Toxicants at ERCs
		5.6.2 DAF-1, DAF-8, DAF-5, and DAF-3 Acted in the Intestine to Regulate the Response to Toxicants at ERCs
		5.6.3 Genetic Interaction DAF-12 and DAF-3 or DAF-5 in Regulating the Response to Toxicants at ERCs
	5.7 Perspectives
	References
Chapter 6: Response of Metabolism-Related Signaling Pathways to Toxicants at Environmentally Relevant Concentrations
	6.1 Introduction
	6.2 Response of MDT-15-Mediated Signaling Pathway to Toxicants at ERCs
		6.2.1 Increase in Fat Storage
		6.2.2 Alteration in Expression of MDT-15 and SBP-1 by Toxicants at ERCs
		6.2.3 Tissue-Specific Activity of MDT-15 and SBP-1 in Regulating the Response to Toxicants at ERCs
		6.2.4 Identification of Downstream Targets of Intestinal SBP-1 in Regulating the Response to Toxicants at ERCs
	6.3 Response of FAT-6-Mediated Signaling Pathway to Toxicants at ERCs
	6.4 Response of NHR-8-Mediated Signaling Pathway to Toxicants at ERCs
		6.4.1 Alteration in NHR-8 Expression by Toxicants at ERCs
		6.4.2 Functional Analysis of NHR-8 in Regulating the Response to Toxicants at ERCs
		6.4.3 Identification of Downstream Targets of NHR-8 in Regulating the Response to Toxicants at ERCs
	6.5 Response of Heme Homeostasis-Related Signaling Pathway to Toxicants at ERCs
		6.5.1 Functional Analysis of GLB-10 in Regulating Toxicity of Toxicants at ERCs
		6.5.2 Downstream Neuronal Targets of GLB-10 in Regulating Toxicity of Toxicants at ERCs
		6.5.3 Downstream Intestinal Targets of GLB-10 in Regulating Toxicity of Toxicants at ERCs
		6.5.4 Interaction Between HRG-7 and HRG-5 in Controlling the Toxicity of Toxicants at ERCs
	6.6 Perspectives
	References
Chapter 7: Response of Protective Response-Related Signaling Pathways to Toxicants at Environmentally Relevant Concentrations
	7.1 Introduction
	7.2 Response of mt UPR-Related Signaling Pathway to Toxicants at ERCs
		7.2.1 Dynamic Alteration in mt UPR Induced by Toxicants at ERCs During the Aging
		7.2.2 Dynamic Alteration in mt UPR Induced by Toxicants at ERCs Under Simulated Microgravity Stress Condition
		7.2.3 Activation of Intestinal mt UPR Response in Nematodes Exposed to Toxicants at ERCs
		7.2.4 Tissue-Specific Activity of HSP-6 in Regulating the Response to Toxicants at ERCs
		7.2.5 Identification of Upstream Regulators of Intestinal mt UPR Activation Induced by Toxicants at ERCs
		7.2.6 Downstream Targets for Intestinal Insulin, Wnt, or ELT-2 Signaling in Controlling Intestinal mt UPR Activation Induced b...
		7.2.7 Interactions Among Intestinal ATFS-1, DVE-1, and UBL-5 in Controlling the Toxicity of Toxicants at ERCs
	7.3 Response of ER UPR-Related Signaling Pathway to Toxicants at ERCs
		7.3.1 Activation of ER UPR by Toxicants at ERCs
		7.3.2 Upstream Regulators of ER UPR Activation Induced by Toxicants at ERCs
			7.3.2.1 XBP-1 Signaling and p38 MAPK Signaling
			7.3.2.2 MDT-15 and SBP-1
			7.3.2.3 Involvement of ER UPR Signaling Pathway in Regulating the Response to Toxicants at ERCs
	7.4 Response of Antimicrobial Proteins to Toxicants at ERCs
		7.4.1 Alteration in Expressions of Antimicrobial Proteins by Toxicants at ERCs
			7.4.1.1 CLEC-63 and CLEC-85
			7.4.1.2 CYP-35A3, CLEC-67, and LYS-7
			7.4.1.3 Intestinal Antimicrobial Proteins
		7.4.2 Upstream Regulators of Antimicrobial Protein Activation Induced by Toxicants at ERCs
			7.4.2.1 ELT-2
			7.4.2.2 FAT-6
		7.4.3 Involvement of Antimicrobial Proteins in Regulating the Response to Toxicants at ERCs
			7.4.3.1 CLEC-63 and CLEC-85
			7.4.3.2 CYP-35A3, CLEC-67, and LYS-7
	7.5 Response of Autophagy-Related Signaling Pathway to Toxicants at ERCs
		7.5.1 Alteration in Autophagy Activation Induced by Toxicants at ERCs
		7.5.2 Upstream Regulators of Autophagy Activation Induced by Toxicants at ERCs
		7.5.3 Involvement of Autophagy-Related Signaling Pathway in Regulating the Response to Toxicants at ERCs
	7.6 Perspectives
	References
Chapter 8: Response of Neurotransmission-Related Molecular Signals to Toxicants at Environmentally Relevant Concentrations
	8.1 Introduction
	8.2 Requirement of Neurotransmission to the Response to Toxicants at ERCs
	8.3 Genes Required for Neurotransmitter Biosynthesis or Transport Regulate the Response to Toxicants at ERCs
		8.3.1 Functions of TBH-1 and CAT-2 in Regulating Response to Toxicants at ERCs
		8.3.2 Functions of TDC-1 and EAT-4 in Regulating Response to Toxicants at ERCs
	8.4 Neurotransmitter Receptors Regulating the Response to Toxicants at ERCs
		8.4.1 Intestinal Neurotransmitter Receptors Regulating the Response to Toxicants at ERCs
		8.4.2 Neuronal Neurotransmitter Receptors Regulating the Response to Toxicants at ERCs
			8.4.2.1 Tyramine Receptors Involved in the Control of Response to Toxicants at ERCs
			8.4.2.2 Glutamate Receptors Involved in the Control of Response to Toxicants at ERCs
	8.5 Downstream Signals of Neurotransmitter Receptors in Regulating the Response to Toxicants at ERCs
		8.5.1 Downstream Signals of Intestinal Neurotransmitter Receptors in Regulating the Response to Toxicants at ERCs
		8.5.2 Downstream Signals of Neuronal Neurotransmitter Receptors in Regulating the Response to Toxicants at ERCs
	8.6 Perspectives
	References
Chapter 9: Response of G Protein-Coupled Receptors and Ion Channels to Toxicants at Environmentally Relevant Concentrations
	9.1 Introduction
	9.2 Response of G Protein-Coupled Receptors to Toxicants at ERCs
		9.2.1 Response of Intestinal G Protein-Coupled Receptors to Toxicants at ERCs
		9.2.2 Response of Neuronal G Protein-Coupled Receptors to Toxicants at ERCs
		9.2.3 Response of Germline G Protein-Coupled Receptors to Toxicants at ERCs
	9.3 Response of G Proteins to Toxicants at ERCs
		9.3.1 Response of Intestinal Gα Subunits to Toxicants at ERCs
		9.3.2 Response of Neuronal Gα Subunits to Toxicants at ERCs
		9.3.3 Response of Germline Gα Subunits to Toxicants at ERCs
	9.4 Response of Ion Channels to Toxicants at ERCs
		9.4.1 Response of Ion Channels to Toxicants at ERCs
		9.4.2 Ion Channels Involved in Controlling Toxicity of Toxicants at ERCs
		9.4.3 Intestinal Ion Channels Involved in Controlling Toxicity of Toxicants at ERCs
		9.4.4 Neuronal Ion Channels Involved in Controlling Toxicity of Toxicants at ERCs
		9.4.5 Targets for Intestinal and Neuronal Ion Channels in Controlling Toxicity of Toxicants at ERCs
	9.5 Perspectives
	References
Chapter 10: Epigenetic Control of Response to Toxicants at Environmentally Relevant Concentrations
	10.1 Introduction
	10.2 miRNAs Control of Response to Toxicants at ERCs
		10.2.1 Response of miRNAs to Toxicants at ERCs
		10.2.2 Functional Analysis of miRNAs in Regulating the Response to Toxicants at ERCs
		10.2.3 Molecular Basis for mir-35 in Regulating the Response to Toxicants at ERCs
		10.2.4 Molecular Basis for mir-794 in Regulating the Response to Toxicants at ERCs
		10.2.5 Molecular Basis for mir-354 in Regulating the Response to Toxicants at ERCs
		10.2.6 Molecular Basis for mir-38 in Regulating the Response to Toxicants at ERCs
		10.2.7 Molecular Basis for mir-76 in Regulating the Response to Toxicants at ERCs
	10.3 lncRNAs Control of Response to Toxicants at ERCs
		10.3.1 Response of lncRNAs to Toxicants at ERCs
		10.3.2 Functional Analysis of lncRNAs in Regulating the Response to Toxicants at ERCs
		10.3.3 Intestinal lncRNAs Required for the Control of Response to Toxicants at ERCs
		10.3.4 Downstream Targets for Intestinal lncRNAs in Controlling the Response to Toxicants at ERCs
	10.4 circRNAs Control of Response to Toxicants at ERCs
		10.4.1 Response of circRNAs to Toxicants at ERCs
		10.4.2 Functional Analysis of circRNAs in Regulating the Response to Toxicants at ERCs
		10.4.3 Functional Analysis of circ_0000115 in Regulating the Response to Toxicants at ERCs
	10.5 Epigenetic Control of Response to Toxicants at ERCs by Histone Methylation-Related Signals
		10.5.1 Response of Histone Methylation-Related Signals to Toxicants at ERCs
		10.5.2 Functional Analysis of MET-2 in Regulating the Response to Toxicants at ERCs
		10.5.3 Tissue-Specific Activity of MET-2 in Regulating the Toxicity of Toxicants at ERCs
		10.5.4 Targets for Intestinal MET-2 in Regulating the Toxicity of Toxicants at ERCs
		10.5.5 Targets for Germline MET-2 in Regulating the Toxicity of Toxicants at ERCs
	10.6 Epigenetic Control of Response to Toxicants at ERCs by Acetylation-Related Signals
		10.6.1 Response of Acetylation-Related Signals to Toxicants at ERCs
		10.6.2 Functional Analysis of Acetylation-Related Signals in Regulating the Response to Toxicants at ERCs
		10.6.3 Tissue-Specific Activity of CBP-1 in Regulating Toxicity of Toxicants at ERCs
		10.6.4 Targets of Intestinal CBP-1 in Regulating Toxicity of Toxicants at ERCs
		10.6.5 Targets of Neuronal CBP-1 in Regulating Toxicity of Toxicants at ERCs
		10.6.6 Targets of Germline CBP-1 in Regulating Toxicity of Toxicants at ERCs
	10.7 Perspectives
	References
Chapter 11: Molecular Networks in Different Tissues in Response to Toxicants at Environmentally Relevant Concentrations
	11.1 Introduction
	11.2 Molecular Network in the Intestine in Regulating Response to Toxicants at ERCs
		11.2.1 Molecular Signaling Network in the Intestine in Response to Toxicants at ERCs
		11.2.2 G Protein-Coupled Receptor (GPCR)-Mediated Molecular Signaling Network in the Intestine in Response to Toxicants at ERCs
		11.2.3 Ion Channel-Mediated Molecular Signaling Network in the Intestine in Response to Toxicants at ERCs
		11.2.4 Epigenetic Control-Mediated Molecular Signaling Network in the Intestine in Response to Toxicants at ERCs
	11.3 Molecular Network in the Neurons in Regulating Response to Toxicants at ERCs
		11.3.1 Molecular Signaling Network in the Neurons in Response to Toxicants at ERCs
		11.3.2 GPCR-Mediated Molecular Signaling Network in the Neurons in Response to Toxicants at ERCs
		11.3.3 Ion Channel-Mediated Molecular Signaling Network in the Neurons in Response to Toxicants at ERCs
		11.3.4 Epigenetic Control-Mediated Molecular Signaling Network in the Neurons in Response to Toxicants at ERCs
	11.4 Molecular Network in the Germline in Regulating Response to Toxicants at ERCs
		11.4.1 Molecular Signaling Network in the Germline in Response to Toxicants at ERCs
		11.4.2 GPCR-Mediated Molecular Signaling Network in the Germline in Response to Toxicants at ERCs
		11.4.3 Epigenetic Control-Mediated Molecular Signaling Network in the Germline in Response to Toxicants at ERCs
	11.5 Signaling Communications Between Different Tissues in Regulating the Response to Toxicants at ERCs
		11.5.1 Signaling Communications Between Neurons and Intestine in Regulating the Response to Toxicants at ERCs
		11.5.2 Signaling Communications Between Germline and Intestine in Regulating the Response to Toxicants at ERCs
		11.5.3 Signaling Communications Between Different Neurons in Regulating the Response to Toxicants at ERCs
	11.6 Basic Conclusions
	11.7 Perspectives
	References
Index