Dataset Information

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis.

ABSTRACT: Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases' responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n?=?107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n?=?75) and to healthy controls (n?=?89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ?Ex3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -??x3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p?

SUBMITTER: Miliaraki M

PROVIDER: S-EPMC7806640 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis.

Miliaraki Marianna M Briassoulis Panagiotis P Ilia Stavroula S Polonifi Aikaterini A Mantzourani Marina M Briassouli Efrossini E Vardas Konstantinos K Nanas Serafim S Pistiki Aikaterini A Theodorakopoulou Maria M Tavladaki Theonymfi T Spanaki Anna Maria AM Kondili Eumorfia E Dimitriou Helen H Tsiodras Sotirios S Georgopoulos Dimitrios D Armaganidis Apostolos A Daikos George G Briassoulis George G

Scientific reports 20210113 1

Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases' responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with trauma ...[more]

PMID: 33441606

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Project description:The cytosolic sulfotransferases (SULTs) metabolize a variety of xenobiotic and endogenous substrates. Several SULTs are expressed in the fetus, implying that these enzymes have important functions during human development. We recently reported that while SULT1C4 mRNA is abundant in prenatal human liver specimens, SULT1C4 protein is barely detectable. Two coding transcript variants (TVs) of SULT1C4 are indexed in GenBank, TV1 (full-length) and TV2 (lacking exons 3 and 4). The purpose of this study was to evaluate expression of the individual TVs as a clue for understanding the discordance between mRNA and protein levels. Reverse-transcription polymerase chain reaction was initially performed to identify TVs expressed in intestinal and hepatic cell lines. This analysis generated fragments corresponding to TV1, TV2, and a third variant that lacked exon 3 (E3DEL). Using reverse-transcription quantitative polymerase chain reaction assays designed to quantify TV1, TV2, or E3DEL individually, all three TVs were more highly expressed in prenatal than postnatal specimens. TV2 levels were ∼fivefold greater than TV1, while E3DEL levels were minimal. RNA sequencing (RNA-seq) analysis of another set of liver specimens confirmed that TV1 and TV2 levels were highest in prenatal liver, with TV2 higher than TV1. RNA-seq also detected a noncoding RNA, which was also more abundant in prenatal liver. Transfection of HEK293T cells with plasmids expressing individual Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys-tagged SULT1C4 isoforms demonstrated that TV1 produced much more protein than did TV2. These data suggest that the lack of correspondence between SULT1C4 mRNA and protein levels in human liver is likely attributable to the inability of the more abundant TV2 to produce stable protein. SIGNIFICANCE STATEMENT: Cytosolic sulfotransferases (SULTs) metabolize a variety of xenobiotic and endogenous substrates, and several SULTs are highly expressed in the fetus, implying that they have important functions during human development. SULT1C4 is highly expressed in prenatal liver at the mRNA level but not the protein level. This study provides an explanation for this discordance by demonstrating that the predominant SULT1C4 transcript is a variant that produces relatively little protein.

Dataset Information

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis.

Publications

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis.

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