The comparison of CHCA solvent compositions for improving LC-MALDI performance and its application to study the impact of aflatoxin B1 on the liver proteome of diabetes mellitus type 1 mice

Abstract

In nanoflow liquid chromatography-matrix-assisted laser desorption/ionization tandem time-of-flight (nanoLC-MALDI-TOF/TOF) approaches, it is critical to directly apply small amounts of the sample elutes on the sample target using a nanoLC system due to its low flow rate of 200 ~ 300 nl/min. It is recommended to apply a sheath liquid containing a matrix with a several μL/min flow rate at the end of the nanoLC column to ensure a larger co-eluted droplet for more reproducible sample spotting and avoid the laborious task of post-manual matrix spotting. In this study, to achieve a better nanoLC-MALDI performance on sample spotting, we first compared α-Cyano-4-hydroxycinnamic acid (CHCA) solvent composition for efficiently concentrating nanoLC elutes on an anchor chip. The solvent composition of isopropanol (IPA): acetonitrile (ACN):acetone:0.1% Trifluoroacetic acid (TFA) (2:7:7:2) provided strong and homogeneous signals with higher peptide ion yields than the other solvent compositions. Then, nanoLC-MALDI-TOF/TOF was applied to study the impact of aflatoxin B1 on the liver proteome from diabetes mellitus type 1 mice. Aflatoxin B1 (AFB1), produced by Aspergillus flavus and Aspergillus parasiticus is a carcinogen and a known causative agent of liver cancer. To evaluate the effects of long-term exposure to AFB1 on type 1 diabetes mellitus (TIDM), the livers of T1DM control mice and mice treated with AFB1 were analyzed using isotope-coded protein labeling (ICPL)-based quantitative proteomics. Our results showed that gluconeogenesis, lipid, and oxidative phosphorylation mechanisms, normally elevated in T1DM, were disordered following AFB1 treatment. In addition, major urinary protein 1 (MUP1), an indicator of increased insulin sensitivity, was significantly decreased in the T1DM/AFB1 group and may have resulted in higher blood glucose levels compared to the T1DM group. These results indicate that T1DM patients should avoid the AFB1 intake, as they could lead to increased blood glucose levels and disorders of energy-producing mechanisms.

Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development

“…To investigate the effects of long-term exposure to AFB1 on type 1 diabetes mellitus (T1DM), some authors analysed the mice livers with T1DM after AFB1 treatment and highlighted that in the T1DM/AFB1 group the levels of the major urinary protein 1 (MUP1) were lower. Hence, considering that MUP1 is used as marker of higher insulin sensitivity, it is clear that AFB1 exposure induces the increased levels of blood glucose in mice and, also, the high probability to develop liver cancer [ 47 ]. Moreover, other studies demonstrated the importance of time intervals between AFB1 exposure and HCC development in absence and in presence of cirrhosis and HBV and evidenced that AFB1 exposure may increase in a dose-response manner the risk to develop cirrhosis and HCC in HBV patients [ 48 ].…”

Barley microgreen incorporation in diet-controlled diabetes and counteracted aflatoxicosis in rats

“…9 Moreover, AFB1 exposure in type 1 diabetic mice disrupted lipid, and oxidative phosphorylation, gluconeogenesis, and reduced major urinary protein 1 (a major insulin sensitivity indicator), with subsequent elevation of blood glucose level. 10 Therefore, the discovery of a new natural intervention becomes crucial. 11 A diet that contains high dietary fiber (DF) can improve the control of DM.…”

Fucoidan Ameliorates Oxidative Stress, Inflammation, DNA Damage, and Hepatorenal Injuries in Diabetic Rats Intoxicated with Aflatoxin B1

“…Although the liver plays vital roles in carbohydrate metabolism and regulation of blood glucose level, it is the target organ for AFB 1 [9]. Intoxication of T1DM mice with AFB 1 -disordered T1DM elevated energy-producing mechanisms, gluconeogenesis, lipid, and oxidative phosphorylation, reduced major urinary protein 1, insulin sensitivity indicator, and subsequently elevated blood glucose level [10]. There is a positive interaction between AFB 1 and diabetes in human subjects [11].…”