DNA Damage and Transcriptional Changes in the Gills of Mytilus galloprovincialis Exposed to Nanomolar Doses of Combined Metal Salts (Cd, Cu, Hg)

Abstract

Aiming at an integrated and mechanistic view of the early biological effects of selected metals in the marine sentinel organism Mytilus galloprovincialis, we exposed mussels for 48 hours to 50, 100 and 200 nM solutions of equimolar Cd, Cu and Hg salts and measured cytological and molecular biomarkers in parallel. Focusing on the mussel gills, first target of toxic water contaminants and actively proliferating tissue, we detected significant dose-related increases of cells with micronuclei and other nuclear abnormalities in the treated mussels, with differences in the bioconcentration of the three metals determined in the mussel flesh by atomic absorption spectrometry. Gene expression profiles, determined in the same individual gills in parallel, revealed some transcriptional changes at the 50 nM dose, and substantial increases of differentially expressed genes at the 100 and 200 nM doses, with roughly similar amounts of up- and down-regulated genes. The functional annotation of gill transcripts with consistent expression trends and significantly altered at least in one dose point disclosed the complexity of the induced cell response. The most evident transcriptional changes concerned protein synthesis and turnover, ion homeostasis, cell cycle regulation and apoptosis, and intracellular trafficking (transcript sequences denoting heat shock proteins, metal binding thioneins, sequestosome 1 and proteasome subunits, and GADD45 exemplify up-regulated genes while transcript sequences denoting actin, tubulins and the apoptosis inhibitor 1 exemplify down-regulated genes). Overall, nanomolar doses of co-occurring free metal ions have induced significant structural and functional changes in the mussel gills: the intensity of response to the stimulus measured in laboratory supports the additional validation of molecular markers of metal exposure to be used in Mussel Watch programs.

Tralopyril bioconcentration and effects on the gill proteome of the Mediterranean mussel Mytilus galloprovincialis

“…All immune-related proteins from DMSO-exposed mussels were downregulated (except MgC1q6, which was upregulated). In accordance with our results, Varotto et al (2013) have also reported downregulation of C1qDC proteins in the gills of mussels exposed to DMSO. Moreover, DMSO was also reported to suppress the immune response in mice (Lin et al, 2015) and salmon (Milston et al, 2003).…”

Adaptation to abiotic stress in the oyster Crassostrea angulata relays on genetic polymorphisms

“…Interestingly, peptidase activity is one of the GO terms with a larger number of polymorphic genes in C. angulata. Therefore, this work shows that mechanisms for responding to stress both by drying and by metal ion pollution in C. angulata imply not only gene regulation, as has been described in mollusks [5,6] but also DNA sequence variations constrained by a selective evolutionary process. Moreover, stressbased modulation of the immune response related to protein kinase activity has been described in mollusk hemocytes [44].…”

“…Specifically, genes needed for protein degradation such as ubiquitin have been found to be more upregulated in the Pyganodon grandis mussel, which is more sensitive to drying, than in the Uniomerus tetralasmus mussel, which is usually found in drying sediments (14.0-fold, versus 2.0-fold) [5]. Also, ubiquitin protein ligases have been shown to be up-regulated in DNA damage regulation process as a response to stress caused by metal salt contamination (Cd, Cu and Hg) in Mytilus galloprovincialis [6].…”

“…Within bivalves, oyster are considered an emerging model in studies of evolution and development, ecology and conservation of Lophotrochozoan [4]. Oysters live in estuarine and intertidal regions, which present changing environments where salinity and temperature fluctuate extensively; they are subject to other important factors including such as desiccation and the presence of toxic metals [5,6]. The oysters is a sessile organism and, such as, plays an important role as biosensor of coastal water pollution but oysters are also of great interest for breeding programs, biotechnological applications and for their commercial value [7,8].…”

Transcriptomic, Biochemical, and Histopathological Responses of the Clam Ruditapes decussatus from a Metal-Contaminated Tunis Lagoon

“…The highest correlation found between Cd tissue levels and lipid peroxidation suggests the involvement of this metal in inducing oxidative stress. Indeed, cadmium can indirectly contribute to oxidative cell stress by displacing Fe and Cu ions from ferritin and other proteins (Varotto et al 2013). It also can displace Zn from metallothioneins and from the active sites of enzymes (e.g., metalloproteinases, lyases, dehydrogenases, SOD), impairing the catalytic, inhibitory, or accessory Zn functions in kinases/phosphatases and zinc-finger proteins (Moulis 2010).…”