Cactus (Opuntia ficus indica) extract improves endoplasmic reticulum stress in Drosophila melanogaster

Abstract

We reported in this paper the requirement of the extract of cactus (Opuntia ficus indica) for regulating unfolded protein response (UPR) target genes and maintaining endoplasmic reticulum (ER) homeostasis. The endoplasmic reticulum (ER) is a subcellular organelle where many proteins are synthesized and sorted to various subcellular destinations. Accumulation of unfolded protein in ER can induce a stress. The ER responds to stress by initiating a cascade of events known as the "unfolded protein response" (UPR). The UPR pathway is triggered by sensors located at the ER membrane. Here, we analyzed a branch of the UPR mediated by ire-1/xbp-1 in Drosophila to establish its regulation by aqueous extract from fruits and cladode of cactus "Opuntia ficus indica". In Drosophila, the Dxbp-1 transcript was submitted to an “unconventional” splicing induced by IRE1 endoribonucease that generated a processed Dxbp-1s transcript encoding a Dxbp-1 protein isoform. The Dxbp-1s is a key regulator in UPR to activate genes involved in folding and degradation to restore ER function. Here, we investigated the interaction between ER stress and bimolecular extract from cactus O. ficus indica which is a xerophyte that play multiple functions in medicine with anti-ulcer, anti-diabetic and antioxidants properties. We showed that the aqueous extract from fruit and cladode of O. ficus indica regulated ER stress mediated by the modulation of the unconventional splicing of mRNA xbp-1 and for transcription of bip RNA. A good correlation was found between ire-1/xbp-1 expression and bip expression.

Key words: ER stress, unfolded protein response (UPR), Drosophila, Dxbp-1 cactus, cladodes, fruit.