Protein synthesis is lowered by 4EBP1 and eIF2-α signaling while protein degradation may be maintained in fasting, hypoxic Amazonian cichlid, <i>Astronotus ocellatus</i>

Cassidy, Alicia A.; Driedzic, William R.; Campos, Derek Felipe; Heinrichs-Caldas, Waldir; Almeida-Val, Vera Maria Fonseca de; Val, Adalberto Luís; Lamarre, Simon G.

doi:10.1242/jeb.167601

Cited by 18 publications

(30 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, growth pathways were downregulated at 15HD, where pERK/ERK and p4E-BP1/4E-BP1 ratios were reduced, suggesting a reduction in protein synthesis and, consequently, an inhibition of growth. Similar effects were observed in teleost fish subjected to hypoxia, where it was determined that a decrease in protein synthesis during hypoxia is likely controlled by signaling molecules such as 4E-BP1 [29]. In the case of ERK, under nutritional stress, the phosphorylation of this molecule was downregulated in fine flounder [30].…”

Section: Discussionsupporting

confidence: 54%

Effects of crowding on the three main proteolytic mechanisms of skeletal muscle in rainbow trout (Oncorhynchus mykiss)

et al. 2020

View full text Add to dashboard Cite

Background: Skeletal muscle is one of the tissues most affected by stress conditions. The protein degradation in this tissue is vital for the supply of energy mediated by different proteolytic pathways such as the ubiquitinproteasome (UPS), autophagy-lysosome (ALS) and the calpain/calpastatin system (CCS). Nevertheless, the regulation of this proteolytic axis under stress conditions is not yet completely clear. Chile is the main producer of rainbow trout (Oncorhynchus mykiss) in the world. This intensive fish farming has resulted in growing problems as crowding and stress are one of the major problems in the freshwater stage. In this context, we evaluated the crowding effect in juvenile rainbow trout kept in high stocking density (30 kg/m 3) for 15, 45 and 60 days, using a control group of fish (10 kg/m 3). Results: Plasmatic cortisol and glucose were evaluated by enzyme immunoassay. The mRNA levels of stress-related genes (gr1, gr2, mr, hsp70, klf15 and redd1), markers of the UPS (atrogin1 and murf1) and CCS (capn1, capn1, cast-l and casts) were evaluated using qPCR. ALS (LC3-I/II and P62/SQSTM1) and growth markers (4E-BP1 and ERK) were measured by Western blot analysis. The cortisol levels increased concomitantly with weight loss at 45 days of crowding. The UPS alone was upregulated at 15 days of high stocking density, while ALS activation was observed at 60 days. However, the CCS was inactivated during the entire trial. Conclusion: All these data suggest that stress conditions, such as crowding, promote muscle degradation in a time-dependent manner through the upregulation of the UPS at early stages of chronic stress and activation of the ALS in long-term stress, while the CCS is strongly inhibited by stress conditions in the rainbow trout muscle farmed during freshwater stage. Our descriptive study will allow perform functional analysis to determine, in a more detailed way, the effect of stress on skeletal muscle physiology as well as in the animal welfare in rainbow trout. Moreover, it is the first step to elucidate the optimal crop density in the freshwater stage and improve the standards of Chilean aquaculture.

show abstract

Section: Discussionsupporting

confidence: 54%

Effects of crowding on the three main proteolytic mechanisms of skeletal muscle in rainbow trout (Oncorhynchus mykiss)

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Protein synthesis can account for 23-42% of a fish's metabolic rate (Cassidy et al, 2018), and it is frequently downregulated under hypoxia to maintain energy homeostasis (Richards, 2009). The decrease in phosphorylation of 4E-BP1 and increase in eIF-2α phosphorylation suggests that protein synthesis is shut down in the liver of AH fish (Fig.…”

Section: Dch Promotes Metabolic Phenotype Switching In the Livermentioning

confidence: 99%

Diel cycling hypoxia enhances hypoxia-tolerance in rainbow trout (Oncorhynchus mykiss): evidence of physiological and metabolic plasticity

Williams

Cassidy

Verhille

et al. 2019

Journal of Experimental Biology

Self Cite

View full text Add to dashboard Cite

Many fish naturally encounter a daily cycle of hypoxia, but it is unclear whether this exposure hardens hypoxia-intolerant fish to future hypoxia or leads to accumulated stress and death. The rainbow trout (Oncorhynchus mykiss) is a putatively hypoxia-sensitive species found in rivers and estuaries that may routinely experience hypoxic events. Trout were exposed to one of four 135 h treatments in a swim-tunnel respirometer: (1) air-saturated control (20.7 kPa P O2 );(2) diel cycling O 2 (20.7-4.2 kPa P O2 over 24 h); (3) acute hypoxia (130 h at 20.7 kPa P O2 followed by 5 h at 4.2 kPa P O2 ); and (4) the mean oxygen tension (12.4 kPa P O2 ) experienced by the diel cycled fish. Some responses were similar in diel O 2 cycled and mean P O2treated fish, but overall, exposure to ecologically representative diel hypoxia cycles improved hypoxia tolerance. Diel hypoxia-induced protective responses included increased inducible HSP70 concentration and mean corpuscular hemoglobin concentration, as well as reduced plasma cortisol. Acclimation to diel hypoxia allowed metabolic rates to decline during hypoxia, reduced oxygen debt following subsequent exposures, and allowed fish to return to an anabolic phenotype. The data demonstrate that acute diel cycling hypoxia improves hypoxia tolerance in previously intolerant fish through the activation of cellular protective mechanisms and a reduction in metabolic O 2 requirements.

show abstract

“…Metabolic suppression during hypoxia can be partially accomplished by suppressing protein metabolism, which includes both protein synthesis and protein degradation. Hypoxia-tolerant species, such as the Amazonian oscar and crucian carp can suppress protein synthesis by as much as 95% in liver and 55% in muscle (Cassidy et al, 2018;Lewis et al, 2007;Smith et al, 1996) during hypoxia, accounting for a 20-36% decrease in metabolism (Cassidy et al, 2018). The adjustments of protein metabolism, if any, have not yet been characterized in hypoxia-sensitive species such as salmonids.…”

Section: Introductionmentioning

confidence: 99%

“…There are three major cellular signalling pathways involved in the hypoxia response: the hypoxia inducible factor (HIF) pathway, the unfolded protein response (UPR) and mTOR pathways (Cassidy et al, 2018;Fang et al, 2015;Wouters and Koritzinsky, 2008). When activated, these pathways eventually inhibit the rate of protein synthesis (Wouters and Koritzinsky, 2008; summarized in Fig.…”

Section: Introductionmentioning

confidence: 99%

Activation of oxygen-responsive pathways are associated with altered protein metabolism in Arctic char exposed to hypoxia

Cassidy

Lamarre

2019

Journal of Experimental Biology

View full text Add to dashboard Cite

Fish exposed to fluctuating oxygen concentrations often alter their metabolism and/or behaviour to survive. Hypoxia tolerance is typically associated with the ability to reduce energy demand by supressing metabolic processes such as protein synthesis. Arctic char is amongst the most sensitive salmonid to hypoxia, and typically engage in avoidance behaviour when faced with lack of oxygen. We hypothesized that a sensitive species will still have the ability (albeit reduced) to regulate molecular mechanisms during hypoxia. We investigated the tissue-specific response of protein metabolism during hypoxia. Little is known about protein degradation pathways during hypoxia in fish and we predict that protein degradation pathways are differentially regulated and play a role in the hypoxia response. We also studied the regulation of oxygen-responsive cellular signalling pathways [hypoxia inducible factor (HIF), unfolded protein response (UPR) and mTOR pathways] since most of what we know comes from studies on cancerous mammalian cell lines. Arctic char were exposed to cumulative graded hypoxia trials for 3 h at four air saturation levels (100%, 50%, 30% and 15%). The rate of protein synthesis was measured using a flooding dose technique, whereas protein degradation and signalling pathways were assessed by measuring transcripts and phosphorylation of target proteins. Protein synthesis decreased in all tissues measured (liver, muscle, gill, digestive system) except for the heart. Salmonid hearts have preferential access to oxygen through a well-developed coronary artery, therefore the heart is likely to be the last tissue to become hypoxic. Autophagy markers were upregulated in the liver, whereas protein degradation markers were downregulated in the heart during hypoxia. Further work is needed to determine the effects of a decrease in protein degradation on a hypoxic salmonid heart. Our study showed that protein metabolism in Arctic char is altered in a tissue-specific fashion during graded hypoxia, which is in accordance with the responses of the three major hypoxia-sensitive pathways (HIF, UPR and mTOR). The activation pattern of these pathways and the cellular processes that are under their control varies greatly among tissues, sometimes even going in the opposite direction. This study provides new insights on the effects of hypoxia on protein metabolism. Adjustment of these cellular processes is likely to contribute to shifting the fish phenotype into a more hypoxia-tolerant one, if more than one hypoxia event were to occur. Our results warrant studying these adjustments in fish exposed to long-term and diel cycling hypoxia.

show abstract

Protein synthesis is lowered by 4EBP1 and eIF2-α signaling while protein degradation may be maintained in fasting, hypoxic Amazonian cichlid, Astronotus ocellatus

Cited by 18 publications

References 48 publications

Effects of crowding on the three main proteolytic mechanisms of skeletal muscle in rainbow trout (Oncorhynchus mykiss)

Effects of crowding on the three main proteolytic mechanisms of skeletal muscle in rainbow trout (Oncorhynchus mykiss)

Diel cycling hypoxia enhances hypoxia-tolerance in rainbow trout (Oncorhynchus mykiss): evidence of physiological and metabolic plasticity

Activation of oxygen-responsive pathways are associated with altered protein metabolism in Arctic char exposed to hypoxia

Contact Info

Product

Resources

About