Degree Type

Dissertation

Date of Award

1996

Degree Name

Doctor of Philosophy

Department

Biochemistry, Biophysics and Molecular Biology

First Advisor

Marit Nilsen-Hamilton

Abstract

Mouse SIP24 was originally discovered as a 24 k Da inducible protein secreted from quiescent Balb/c 3T3 fibroblast cells. Based on the analysis of peptide sequencing results and Western blot studies, SIP24 was identified as identical to the mouse protein encoded by 24P3 and is thus referred to as SIP24/24P3 in this thesis. SIP24/24P3 is a member of the lipocalin protein family, and its human homolog NGAL (neutrophil gelatinase associated lipocalin) has been reported to bind the chemotactic factor, fMLP (N-formylmethionyl-leucyl-phenylalanine);Studies were carried out to test the hypothesis that SIP24/24P3 is an acute phase protein (APP) like some other lipocalins. During the turpentine-induced acute phase response, the level of SIP24/24P3 messenger RNA increased dramatically in liver, and its protein product was detected in the serum. Under similar conditions, dexamethasone induced a relatively moderate increase in SIP24/24P3 mRNA in the liver. The results indicate that SIP24/24P3 is a new acute phase protein and may be involved in the systemic host inflammatory response;A tissue distribution study showed that during the turpentine induced acute phase response, SIP24/24P3 is expressed in the liver, uterus and brain. The liver is the major site of SIP24/24P3 mRNA expression. The results of the hepatic regulation pattern indicate that SIP24/24P3 is a type-1 acute phase protein because its protein can only be induced by TNF-[alpha] but not IL-6 in cultured BNL (Balb/c normal liver) cells;SIP24/24P3 was also found to be expressed in the liver and uterus during midgestation. A time course study was carried out to determine the expression of SIP24/24P3 during pregnancy and around parturition. SIP24/24P3 message was expressed at high levels in uterus around birth. Meanwhile, contrary to its expression pattern during the acute phase response, SIP24/24P3 was not expressed significantly in the liver. Examination of the presence of its protein in body fluids revealed that SIP24/24P3 protein was undetectable in the bloodstream or amniotic fluid in spite of the massive expression of its mRNA in uterus. The results suggest that SIP24/24P3 is expressed locally in the uterus and may participate in the local inflammatory response around birth.

DOI

https://doi.org/10.31274/rtd-180813-10229

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/

Copyright Owner

Quansheng Liu

Language

en

Proquest ID

AAI9620978

File Format

application/pdf

File Size

97 pages

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