Edited by Francesc PosasKeywords: Rck1 Yap2 Cadmium MAPK-activated protein Yeast a b s t r a c t Yap2 is a cadmium responsive transcription factor that interacts with MAPK-activated protein (MAPKAP) kinase Rck1. We show that Rck1 deletion confers protection against cadmium toxicity and that the mechanism underlying this observation relies on Yap2. Rck1 removal from the yeast genome potentiates Yap2 activity by increasing protein half-life and delaying its nuclear export. As a consequence, several Yap2 antioxidant targets are over-activated by a mechanism that also requires Yap1. Several genes of the cell wall integrity (CWI) pathway are upregulated under cadmium stress in a Yap2 dependent way. We showed that deletion of CWI genes renders yeast cells more sensitive to cadmium. These findings led us to suggest that in response to cadmium stress Yap2 may serve a dual purpose: oxidative stress attenuation and cell wall maintenance.

Polyphenols are natural compounds present in fruits and vegetables that can exert beneficial effects on human health and notably, on the cardiovascular system. Some of these compounds showed significant protective activities toward atherosclerosis, hypertension, myocardial infarction, anthracyclin-induced cardiomyopathy, angiogenesis as well as heart failure. Polyphenols can act through systemic effects as well as through modulation of signaling pathways such as redox signaling, inflammation, autophagy and cell death in the heart and vessels. These effects can be mediated by changes in expression level and by post-translational modifications of proteins (e.g. Stat1, CaMKII, Sirtuins, BCL-2 family members, PDEs, TRF2, eNOS and SOD). This non-comprehensive short review aims to summarize recent knowledge on the main pharmacological effects and mechanisms of cardioprotection of pure polyphenols, using different approaches such as cell culture, animal models and human studies.

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The association between altered proteostasis and inflammatory responses has been increasingly recognized, therefore the identification and characterization of novel compounds with anti-inflammatory potential will certainly have a great impact in the therapeutics of protein-misfolding diseases such as degenerative disorders. Although cell-based screens are powerful approaches to identify potential therapeutic compounds, establishing robust inflammation models amenable to high-throughput screening remains a challenge. To bridge this gap, we have exploited the use of yeasts as a platform to identify lead compounds with anti-inflammatory properties. The yeast cell model described here relies on the high-degree homology between mammalian and yeast Ca(2+)/calcineurin pathways converging into the activation of NFAT and Crz1 orthologous proteins, respectively. It consists of a recombinant yeast strain encoding the lacZ gene under the control of Crz1-recongition elements to facilitate the identification of compounds interfering with Crz1 activation through the easy monitoring of β-galactosidase activity. Here, we describe in detail a protocol optimized for high-throughput screening of compounds with potential anti-inflammatory activity as well as a protocol to validate the positive hits using an alternative β-galactosidase substrate.