Lipid Rafts Disruption Increases Ochratoxin A Cytotoxicity to Hepatocytes

Abstract

Lipid rafts are microdomains in plasma membrane and can mediate cytotoxicity. In this study, the role of lipid rafts in ochratoxin A-induced toxicity was investigated using Hepatoblastoma Cell Line HepG-2 cells. Disruption of cholesterol-containing lipid rafts enhanced Ochratoxin A (OTA) toxicity, as shown by increased lactate dehydrogenase leakage, increased reactive oxygen species level and reduction of superoxide dismutase activity in a time-dependent manner. Isobaric tags for relative and absolute quantitation-based proteomics of the cell membranes showed that nearly 85.5% proteins were downregulated by OTA, indicating that OTA inhibited the membrane protein synthesis. Most of altered proteins were involved in Gene Ontology "transport", "cell adhesion" and "vesicle-mediated transport". In conclusion, lipid rafts play a key role in OTA-induced cytotoxicity. This study provides insight into how OTA toxicity is regulated by the plasma membrane, especially the lipid rafts.

Lipid rafts are required for effective renal D1dopamine receptor function

“…We next evaluated the presence of oxidative stress by measuring the levels of urinary isoprostanes 42 in β‐MCD‐treated mice and found that the urinary levels were increased compared with control (vehicle‐ and α‐MCD‐treated) mice (Figure 7A). Disruption of lipid rafts and lipid raft clustering are associated with oxidative stress in glomerular epithelial cells and hepatocytes 43‐45 but not breast cancer cells. β‐MCD facilitates the hepatoxicity of ochratoxin 45 .…”

“…Disruption of lipid rafts and lipid raft clustering are associated with oxidative stress in glomerular epithelial cells and hepatocytes 43‐45 but not breast cancer cells. β‐MCD facilitates the hepatoxicity of ochratoxin 45 . Therefore, we further explored the role of lipid raft residency of D 1 R on oxidative stress in mouse RPTCs and found that β‐MCD treatment doubled the production of ROS in the treated cells, indicating the presence of heightened oxidative stress when the lipid rafts were perturbed (Figure 7B,C).…”

The importance of accounting for sex in the search of proteomic signatures of mycotoxin exposure

“…Other study investigated the effect of OTA in the composition of the hepatoblastoma cell line HepG-2 plasma membrane [87]. This showed that OTA induced a loss of more than 85% of hepatotoxicity [87].…”

“…Other study investigated the effect of OTA in the composition of the hepatoblastoma cell line HepG-2 plasma membrane [87]. This showed that OTA induced a loss of more than 85% of hepatotoxicity [87]. HepG2 cells were originally derived from a male patient's liver, and so the same results in liver cells derived from a female patient remain to be confirmed.…”

A Lateral Flow Strip Based Aptasensor for Detection of Ochratoxin A in Corn Samples

“…Due to its chemical stability during food and feed processing, OTA may reside in foodstuff, spices and animal feed [ 8 , 9 , 10 , 11 ]. In addition, OTA is a nephrotoxic toxin [ 12 ] with strong carcinogenic effects on rodents [ 13 ]. OTA has been proven to be teratogenic, embryotoxic, genotoxic, neurotoxic and immunosuppressive [ 14 , 15 ].…”