Heat shock proteins and hypometabolism: adaptive strategy for proteome preservation

SUMMARYPreservation of muscle morphology depends on a continuing regulatory balance between molecules that protect and molecules that damage muscle structural integrity. Excessive disruption of the biochemical balance that favours reactive oxygen species (ROS) in disused muscles may lead to oxidative stress, which in turn is associated with increased atrophic or apoptotic signalling and/or oxidative damage to the muscle and thus muscle disuse atrophy. Increases in the rate of oxygen consumption likely increase the overall generation of ROS in vivo. Temperature-induced increases in oxygen consumption rate occur in some muscles of ectotherms undergoing prolonged muscular disuse during aestivation. In the green-striped burrowing frog, Cyclorana alboguttata, both large jumping and small non-jumping muscles undergo atrophy seemingly commensurate with their rate of oxygen consumption during aestivation. However, because the extent of atrophy in these muscles is not enhanced at higher temperatures, despite a temperature-sensitive rate of oxygen consumption in the jumping muscle, we proposed that muscles are protected by biochemical means that, when mobilised at higher temperatures, inhibit atrophy. We proposed that the biochemical response to temperature would be muscle-specific. We examined the effect of temperature on the antioxidant and heat shock protein systems and determined the extent of oxidative damage to lipids and proteins in two functionally different skeletal muscles, the gastrocnemius (jumping muscle) and the iliofibularis (non-jumping muscle), by aestivating frogs at 24 and 30°C for 6months. We assayed small molecule antioxidant capacity, mitochondrial and cytosolic superoxide dismutase activities and Hsp70 concentrations to show that protective mechanisms in disused muscles are differentially regulated with respect to both temperature and aestivation. High aestivation temperature results in an antioxidant response in the metabolically temperaturesensitive jumping muscle. We assayed lipid peroxidation and protein oxidation to show that oxidative damage is apparent during aestivation and its pattern is muscle-specific, but unaffected by temperature. Consideration is given to how the complex responses of muscle biochemistry inform the different strategies muscles may use in regulating their oxidative environment during extended disuse and disuse at high temperature.

Section: Hsp70mentioning

confidence: 99%

Each to their own: skeletal muscles of different function use different biochemical strategies during aestivation at high temperature

Young

Cramp

Franklin

2012

“…Strong metabolic rate depression during aestivation minimizes energy use to prolong total survival time, but this also means that the normal turnover of macromolecules (synthesis and degradation) is much reduced so that preservation strategies are needed to extend their functional lifespans. This is provided by mechanisms including enhanced antioxidant defenses and elevated chaperone proteins, strategies that are well-known components of the stress response (Kültz, 2005) but are also widely used across all forms of natural hypometabolism to support viability and life extension Storey and Storey, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…intermediary metabolism, membrane transport, protein synthesis, gene expression, etc. ), a reprioritization of ATP use to favour vital functions, a transition to a reliance on stored reserves of body fuels, and the implementation of cell preservation mechanisms such as antioxidant defenses and chaperones Storey and Storey, 2011). Overlaid on these are adaptations that deal with the specific issues and/or stresses surrounding each phenomenon.…”

Section: Introductionmentioning

confidence: 99%

Aestivation: signaling and hypometabolism

Storey

2012

137

116

SummaryAestivation is a survival strategy used by many vertebrates and invertebrates to endure arid environmental conditions. Key features of aestivation include strong metabolic rate suppression, strategies to retain body water, conservation of energy and body fuel reserves, altered nitrogen metabolism, and mechanisms to preserve and stabilize organs, cells and macromolecules over many weeks or months of dormancy. Cell signaling is crucial to achieving both a hypometabolic state and reorganizing multiple metabolic pathways to optimize long-term viability during aestivation. This commentary examines the current knowledge about cell signaling pathways that participate in regulating aestivation, including signaling cascades mediated by the AMPactivated kinase, Akt, ERK, and FoxO1.

“…Many organisms that transition through states of reduced metabolic rate exhibit alterations in their cellular detoxification and cytoprotective pathways as a means of viability extension (Storey, 1996;Storey and Storey, 2011). In D. gigas, the antioxidant capacity decreased significantly in three tissues (mantle muscle, branchial heart and brain).…”

Section: Research Articlementioning

confidence: 99%

“…Transcriptional regulation factors and translation initiation and elongation factors are known to be important in other models of metabolic rate depression (Larade and Storey, 2002;Hittel and Storey, 2002;Morin and Storey, 2006;Krivoruchko and Storey, 2010a;Krivoruchko and Storey, 2010b;Krivoruchko and Storey, 2010c;Tessier and Storey, 2010) and were targeted in the present study as molecular indices of transcriptional and translational suppression. Despite global suppression of transcription and translation, a common organismal response to environmental stress includes concomitant increases in stress-responsive pathways such as antioxidant defenses and heat shock proteins (HSP) (Storey, 1996;Storey and Storey, 2011;Trübenbach et al, 2012b). As hypoxia-tolerant organisms reduce ATP demand by reducing biosynthetic functions, a greater emphasis may be placed on these macromolecule-preservation strategies.…”

Section: Introductionmentioning

confidence: 99%

Metabolic suppression during protracted exposure to hypoxia in the jumbo squid,Dosidicus gigas, living in an oxygen minimum zone

Seibel

Häfker

Trübenbach

et al. 2014

The jumbo squid, Dosidicus gigas, can survive extended forays into the oxygen minimum zone (OMZ) of the Eastern Pacific Ocean. Previous studies have demonstrated reduced oxygen consumption and a limited anaerobic contribution to ATP production, suggesting the capacity for substantial metabolic suppression during hypoxic exposure. Here, we provide a more complete description of energy metabolism and explore the expression of proteins indicative of transcriptional and translational arrest that may contribute to metabolic suppression. We demonstrate a suppression of total ATP demand under hypoxic conditions (1% oxygen, P O2 =0.8 kPa) in both juveniles (52%) and adults (35%) of the jumbo squid. Oxygen consumption rates are reduced to 20% under hypoxia relative to airsaturated controls. Concentrations of arginine phosphate (Arg-P) and ATP declined initially, reaching a new steady state (~30% of controls) after the first hour of hypoxic exposure. Octopine began accumulating after the first hour of hypoxic exposure, once Arg-P breakdown resulted in sufficient free arginine for substrate. Octopine reached levels near 30 mmol g −1 after 3.4 h of hypoxic exposure. Succinate did increase through hypoxia but contributed minimally to total ATP production. Glycogenolysis in mantle muscle presumably serves to maintain muscle functionality and balance energetics during hypoxia. We provide evidence that post-translational modifications on histone proteins and translation factors serve as a primary means of energy conservation and that select components of the stress response are altered in hypoxic squids. Reduced ATP consumption under hypoxia serves to maintain ATP levels, prolong fuel store use and minimize the accumulation of acidic intermediates of anaerobic ATP-generating pathways during prolonged diel forays into the OMZ. Metabolic suppression likely limits active, daytime foraging at depth in the core of the OMZ, but confers an energetic advantage over competitors that must remain in warm, oxygenated surface waters. Moreover, the capacity for metabolic suppression provides habitat flexibility as OMZs expand as a result of climate change.