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Effects of high molecular weight phthalates on LPS-stimulated THP-1 macrophages - phosphoproteome

ABSTRACT: In this study, the effects of three high molecular weight phthalates (DINP, DIDP, DPHP) and their metabolites (MHINP, MCINP, OHMPHP) were investigated in THP-1 macrophages. For this purpose, the phosphoproteome was evaluated.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Isabel Karkossa

LAB HEAD: Kristin Schubert

PROVIDER: PXD042912 | Pride | 2023-09-13

REPOSITORIES: Pride

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Source:

			Action	DRS
	20220304_Uniprot_HomoSapiens_Refset.fasta	Fasta
	DIDP_MCINP_PP_01.raw	Raw
	DIDP_MCINP_PP_02.raw	Raw
	DIDP_MCINP_PP_03.raw	Raw
	DIDP_MCINP_PP_04.raw	Raw

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Project description:Transcriptional profiling of rat liver comparing male rats with congenital hypothyrodism (CH) vs intact at adulhood. Here we studied how CH influences liver gene expression program in adulthood. Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology but its specific influence in liver is less understood. Here we studied how CH influences liver gene expression program in adulthood. Pregnant rats were given anti-thyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as a reduction in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, feed efficiency increased in CH and this was accompanied by significant catch-up growth. On PND80, significant reduction in body mass, tail length, and circulating IGF-I remained in CH rats. On the other hand, mRNA levels of known GH targeted genes were significantly up-regulated. Serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in expression for hepatic genes involved in lipid metabolism with an increased transcription of PPAR and reduced expression of genes involved in fatty acids and cholesterol uptake, cellular sterol efflux, triglycerides assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to hypothyroidism onset in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters, and to T3 replacement with enhanced activation of lipogenic transcriptional program. In summary, we provided in vivo evidence that neonatal hypothyroidism causes long-lasting effects on hepatic transcriptional program and tissue sensitivity to hormone treatment. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood. Two conditions CH vs INTACT male rats. Biological replicates: Four independent hybridizations: 4 controls (age-matched intact rats) vs 4 CH (male rats with congenital hypothyroidism) on postnatal day 80 for a total of four arrays. One replicate per array.

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Effects of high molecular weight phthalates on LPS-stimulated THP-1 macrophages - phosphoproteome

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