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Neuronal ire-1 coordinates an organism-wide cold stress response by regulating fat metabolism - Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and ire-1(ok799) Transcriptomes During Cold Stress.

ABSTRACT: Cold affects many aspects of biology, medicine, agriculture and industry. Here, we identify a conserved endoplasmic reticulum (ER) stress response, distinct from the canonical unfolded protein response, which maintains lipid homeostasis during extreme cold stress. We establish that the ER stress sensor IRE-1 is critical for resistance to extreme cold and is activated by cold temperature. Specifically, neuronal IRE-1 signals via JNK-1 and neuropeptide-mediated signalling to regulate lipid composition throughout the animal. The requirement of this cold-response pathway can be bypassed by supplementation with unsaturated fatty acids or by altering the diet . Altogether, our findings define an ER-centric conserved organism-wide cold stress response pathway, consisting of sensors, effectors and signalling moieties, which control adaptation to cold throughout the organism. Better understanding of the molecular basis of cold adaptation is crucial for the design of safe and optimal use of cold conditions on live organisms and samples, and for the development of better treatments for hypothermia. Conclusions: Our study represents a detailed analysis of C.elegans transcriptomes during cold stress, with biological replicates, generated by RNA-seq technology.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE193923 | GEO | 2022/11/15

REPOSITORIES: GEO

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Project description:Stress leads to important adaptive physiological responses including release of catecholamines from the adrenal medulla. Repeated or prolonged stress increases the propensity for many disorders including cardiovascular disease and neuropsychiatric disorders. The susceptibility to stress is determined by a number of factors including prior experience with stress. It has been found that while there is adaptation to prolonged cold stress; it leads to sensitization when cold stressed animals are exposed to a different (novel) stressor. Our study aims to determine the mechanism of this adaptation and sensitization.,We will determine the gene expression patterns in rat adrenal medulla in response to several times of cold stress. We will also determine the changes in gene expression with single immobilization stress in adrenal medulla of rat with and without preexposure to cold stress to investigate the mechanism of sensitization in cold adapted animals. ,We hypothesize that during the course of cold stress there are alterations in gene expression of several neurotransmitter related genes and transcription factors. In cold adapted animals, there is increased susceptibility to stress due to sustained changes in expression of several transcription factors, such as FRA-2 which lead to an exaggerated response to the novel stressor. ,Rats were exposed to cold stress (4oC) for 1, 7 or 28 days. A parallel group was kept at room temperature (unstressed). Unstressed or rats pre-exposed to 28 days cold were immobilized for 2 hrs and killed by decapitation. The adrenal medullae, separately from right and left side, have been dissected and individually frozen at -70oC. Our recent immunoblots with the tissue from one side revealed that there is increase in tyrosine hydroxylase and c-fos with the short term cold stress and in dopamine beta hydroxylase and Fra-2 even with the prolonged cold stress. The response of several transcription factors to immobilization stress was enhanced in the cold adapted animals. RNA will be prepared with RNAqueous-Micro Isolation kit from Ambion (alternatively we can ship the tissues). We will pool samples from 4 rats per treatment to control for variability.

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Neuronal ire-1 coordinates an organism-wide cold stress response by regulating fat metabolism - Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and ire-1(ok799) Transcriptomes During Cold Stress.

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