👤 Arthur H Moser

Actin is a protein of central importance to many cellular functions. Its localization and activity are regulated by interactions with a high number of actin-binding proteins. In a yeast two-hybrid (Y2H) screening system, snail family transcriptional repressor 2 (SNAI2 or slug) was identified as a yet unknown potential actin-binding protein. We validated this interaction using immunoprecipitation and analyzed the functional relation between slug and actin. Since both proteins have been reported to be involved in DNA double-strand break (DSB) repair, we focused on their interaction during this process after treatment with doxorubicin or UV irradiation. Confocal microscopy elicits that the overexpression of actin fused to an NLS stabilizes complexes of slug and γH2AX, an early marker of DNA damage repair. Show less

Leptin (LEP) can cross the blood-brain barrier and facilitate cross-talk between the adipose tissue and central nerve system (CNS). This study aimed to investigate the effect of 8-week high-intensity interval training (HIIT) on the LEP signaling in the hippocampus of rats with type 2 diabetes. 20 rats were randomly divided into four groups: (i) control (Con), (ii) type 2 diabetes (T2D), (iii) exercise (EX), and (iv) type 2 diabetes + exercise (T2D + EX). The rats in the T2D and T2D + EX were fed a high-fat diet for two months, then a single dose of STZ (35 mg/kg) was injected to induce diabetes. The EX and T2D + EX groups performed 4-10 intervals of treadmill running at 80-100% of V Show less

Carbohydrate response element binding protein (ChREBP) is a recently discovered transcription factor whose levels and activity are increased by glucose leading to the activation of target genes, which include acetyl-CoA carboxylase, fatty acid synthase, and liver-type pyruvate kinase. Here, we demonstrate that lipopolysaccharide (LPS) treatment causes a marked decrease in ChREBP mRNA and protein levels in the liver of mice fed a normal chow diet or in mice fasted for 24 h and then re-fed a high carbohydrate diet. This decrease occurs rapidly and is a sensitive response (half-maximal dose 0.1 μg/mouse). The decrease in ChREBP is accompanied by a decrease in the expression of ChREBP target genes. Zymosan and turpentine treatment also decrease hepatic ChREBP levels and the expression of its target genes. Additionally, tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) decrease liver ChREBP expression both in vivo and in Hep3B cells in culture. Finally, LPS decreased ChREBP expression in muscle and adipose tissue. These studies demonstrate that ChREBP is down-regulated during the acute phase response resulting in alterations in the expression of ChREBP regulated target genes. Thus, ChREBP joins a growing list of transcription factors that are regulated during the acute phase response. Show less

Infection and inflammation are associated with atherosclerosis. During infection and inflammation, HDL decreases and there are changes in the levels of several HDL-associated proteins. To identify changes in the protein composition of HDL during infection and inflammation, a proteomic approach was utilized. Using two-dimensional gel electrophoresis and mass spectrometry, we found the expected increases in apolipoprotein (apo) SAA and apo E, as well as a decrease in apo A-I on HDL isolated from mice injected with endotoxin. We identified apo A-IV and apo A-V as positive acute-phase proteins in mouse HDL. We also found an increase in hepatic mRNA levels of apo A-IV and apo A-V after injection of endotoxin. Interleukin-6 increased apo A-IV and apo A-V mRNA levels in Hep3B cells. Additionally, we demonstrated that the protein levels of apo A-II in acute-phase HDL and the hepatic mRNA levels of apo A-II were decreased. Apo A-IV and A-V are positive acute-phase proteins that increase in the serum during inflammation while apo A-II is a negative acute-phase protein in mice. Similar to other positive and negative acute-phase proteins, changes in hepatic production account for the changes in serum levels. However, the changes in apo A-IV and apo A-V, two apolipoproteins whose activities are not fully understood, may serve functions other than regulating lipid metabolism during the acute-phase response (APR). Coupled with the other changes in HDL proteins that occur, these changes are likely to alter the functional properties of HDL perhaps increasing the risk of atherosclerosis. Show less