Fumonisin B2 Induces Mitochondrial Stress and Mitophagy in Human Embryonic Kidney (Hek293) Cells-A Preliminary Study.

Jivanka Mohan,Anil A Chuturgoon,Terisha Ghazi,Naeem Sheik Abdul,Savania Nagiah

doi:10.3390/toxins14030171

Jivanka Mohan, Anil A Chuturgoon + Show 3 more

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https://doi.org/10.3390/toxins14030171

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Abstract

Ubiquitous soil fungi parasitise agricultural commodities and produce mycotoxins. Fumonisin B2 (FB2), the structural analogue of the commonly studied Fumonisin B1 (FB1), is a neglected mycotoxin produced by several Fusarium species. Mycotoxins are known for inducing toxicity via mitochondrial stress alluding to mitochondrial degradation (mitophagy). These processes involve inter-related pathways that are regulated by proteins related to SIRT3 and Nrf2. This study aimed to investigate mitochondrial stress responses in human kidney (Hek293) cells exposed to FB2 for 24 h. Cell viability was assessed via the methylthiazol tetrazolium (MTT) assay, and the half-maximal inhibitory concentration (IC50 = 317.4 µmol/L) was estimated using statistical software. Reactive oxygen species (ROS; H2DCFDA), mitochondrial membrane depolarisation (JC1-mitoscreen) and adenosine triphosphate (ATP; luminometry) levels were evaluated to assess mitochondrial integrity. The relative expression of mitochondrial stress response proteins (SIRT3, pNrf2, LONP1, PINK1, p62 and HSP60) was determined by Western blot. Transcript levels of SIRT3, PINK1 and miR-27b were assessed using quantitative PCR (qPCR). FB2 reduced ATP production (p = 0.0040), increased mitochondrial stress marker HSP60 (p = 0.0140) and suppressed upregulation of mitochondrial stress response proteins SIRT3 (p = 0.0026) and LONP1 (p = 0.5934). FB2 promoted mitophagy via upregulation of pNrf2 (p = 0.0008), PINK1 (p = 0.0014) and p62 (p < 0.0001) protein expression. FB2 also suppressed miR-27b expression (p < 0.0001), further promoting the occurrence of mitophagy. Overall, the findings suggest that FB2 increases mitochondrial stress and promotes mitophagy in Hek293 cells.

Highlights

Favourable weather conditions cause ubiquitous soil fungi to parasitise agricultural commodities and produce mycotoxins [1]
Limited biochemical studies exist demonstrating the effects of fumonisins in the human kidney
Apart from the canonical mechanism of sphingolipid metabolism disruption [16], little is known about Fumonisin B2 (FB2) -induced toxicity

Summary

Introduction

Favourable weather conditions cause ubiquitous soil fungi to parasitise agricultural commodities and produce mycotoxins [1]. Ingestion of mycotoxin-contaminated food can induce adverse effects on the health of the consumer. Mycotoxin consumption is associated with acute and chronic toxicity in both humans and animals [1,2]. Fumonisin B2 (FB2 ) is the structural analogue of the popularly studied fumonisin B1. Fumonisins are highly prevalent toxins produced mainly by the Fusarium species, a common contaminant of maize [3]. These mycotoxins have been classified by the International Agency for Research on Cancer as class 2B carcinogens, indicating potential toxicity to humans [4]. The toxin exerts its adverse effects in humans via numerous pathways, including induction of apoptosis, oxidative stress, mitochondrial dysfunction, and epigenetic modifications [9–12]

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