Meta-analysis of heat- and chemically upregulated chaperone genes in plant and human cells

Abstract

Molecular chaperones are central to cellular protein homeostasis. In mammals, protein misfolding diseases and aging cause inflammation and progressive tissue loss, in correlation with the accumulation of toxic protein aggregates and the defective expression of chaperone genes. Bacteria and non-diseased, non-aged eukaryotic cells effectively respond to heat shock by inducing the accumulation of heat-shock proteins (HSPs), many of which molecular chaperones involved in protein homeostasis, in reducing stress damages and promoting cellular recovery and thermotolerance. We performed a meta-analysis of published microarray data and compared expression profiles of HSP genes from mammalian and plant cells in response to heat or isothermal treatments with drugs. The differences and overlaps between HSP and chaperone genes were analyzed, and expression patterns were clustered and organized in a network. HSPs and chaperones only partly overlapped. Heat-shock induced a subset of chaperones primarily targeted to the cytoplasm and organelles but not to the endoplasmic reticulum, which organized into a network with a central core of Hsp90s, Hsp70s, and sHSPs. Heat was best mimicked by isothermal treatments with Hsp90 inhibitors, whereas less toxic drugs, some of which nonsteroidal anti-inflammatory drugs, weakly expressed different subsets of Hsp chaperones. This type of analysis may uncover new HSP-inducing drugs to improve protein homeostasis in misfolding and aging diseases.

HsfA2 Controls the Activity of Developmentally and Stress-Regulated Heat Stress Protection Mechanisms in Tomato Male Reproductive Tissues

“…In general, our transcriptome analysis revealed a lower number of stress-induced genes compared to other studies (Finka et al, 2011;Liu and Charng, 2013;Rizhsky et al, 2004). This on one hand can be attributed to the high stringency criteria we used here for the identification of differentially expressed genes and, on the other hand, on the fact that stressed samples were harvested after 1.5 h of recovery.…”

“…HSR requires a complex network of distinct and interconnected pathways involved in maintenance of protein homeostasis, reduction of cellular damages, and readjustment of metabolic activities. Genes encoding for heat shock proteins (Hsps), such as molecular chaperones, are the best studied HS-induced genes, but a plethora of other genes are upregulated to contribute to HSR as shown by transcriptome analysis in several plant species (Finka et al, 2011;Jung et al, 2012;Liu and Charng, 2013;Sarkar et al, 2014;Fragkostefanakis et al, 2015b). The rapid and strong transcriptional activation of the majority of genes is controlled by the activity of the heat stress transcription factors (Hsfs).…”

Plasma Membrane Cyclic Nucleotide Gated Calcium Channels Control Land Plant Thermal Sensing and Acquired Thermotolerance

“…Whereas most molecular chaperones can prevent protein aggregation, some can use ATP to convert already misfolded and aggregated proteins into unfolded polypeptides that can recover their native conformation after the stress (Sharma et al, 2010) or become degraded by ATP-regulated proteases (Hinault et al, 2011). The sHsps are of particular interest to the understanding of the molecular basis for plant-acquired thermotolerance because they are among the most strongly expressed Hsps during a heat priming treatment (Mittler et al, 2012) and their accumulation in various cellular compartments correlates with acquired thermotolerance (Dafny-Yelin et al, 2008;Larkindale and Vierling, 2008;Finka et al, 2011). Their mode of action involves both membrane and protein protection: sHsps form large oligomers (Stengel et al, 2010) that during heat stress transiently dissociate into amphiphilic dimers, which upon inserting into lipid bilayers may stabilize hyperfluidized membranes (Tsvetkova et al, 2002).…”

The role of small GTPase Rac1 in stress signaling

“…HSPs thus promote the cellular recovery and the development of thermotolerance (Calderwood et al 2010;Finka et al 2011). HSP molecular chaperones play several important roles in protein homeostasis through the following processes:…”

“…GroEL is a double-ring 14mer and GroES is a single-ring heptamer that binds to GroEL in the presence of ATP. In the eukaryotic cytosol the more poorly characterized TRiC Moreover, autophagy-mediated degradation of protein aggregates is induced by HSP22 (Horváth et al 2008;Finka et al 2011;Niforou et al 2014). sHsps are also reported to be HSP expression is a transcriptionally controlled process.…”