Untitled

Abstract

The total Ca-ATPase activity in the sarcoplasmic reticulum (SR) membrane fraction isolated from skeletal muscles of winter hibernating ground squirrel Spermophilus undulatus is approximately 2.2-fold lower than in preparations obtained from summer active animals. This is connected in part with approximately 10% decrease of the content of Ca-ATPase protein in SR membranes. However, the enzyme specific activity calculated with correction for its content in SR preparations is still approximately 2-fold lower in hibernating animals. Analysis of the protein composition of SR membranes has shown that in addition to the decrease in Ca-ATPase content in hibernating animals, the amount of SR Ca-release channel (ryanodine receptor) is decreased approximately 2-fold, content of Ca-binding proteins calsequestrin, sarcalumenin, and histidine-rich Ca-binding protein is decreased approximately 3-4-fold, and the amount of proteins with molecular masses 55, 30, and 22 kD is significantly increased. Using the cross-linking agent cupric-phenanthroline, it was shown that in SR membranes of hibernating ground squirrels Ca-ATPase is present in a more aggregated state. The affinity of SR membranes to the hydrophilic fluorescent probe ANS is higher and the degree of excimerization of the hydrophobic probe pyrene is lower (especially for annular lipids) in preparations from hibernating than from summer active animals. The latter indicates an increase in the microviscosity of the lipid environment of Ca-ATPase during hibernation. We suggest that protein aggregation as well as the changes in protein composition and/or in properties of lipid bilayer SR membranes can result in the decrease of enzyme activity during hibernation.

Mammalian hibernation: differential gene expression and novel application of epigenetic controls

“…Some of the major ATP-consuming processes in cells include transmembrane ion transport, gene transcription, and protein translation and, not surprisingly, the rates of all of these processes as well as of fuel catabolism and many other metabolic functions are strongly suppressed when hibernators enter torpor (Frerichs et al, 1998;MacDonald and Storey, 1999;van Breukelen and Martin, 2002;Storey, 2004, 2007). For example, plasma membrane Na + K + -ATPase activity was reduced by 60% during hibernation (MacDonald and Storey, 1999) and the activity of sarco(endo)plasmic reticulum Ca 2+ -ATPase as well as the levels of other proteins associated with calcium signaling were similarly reduced (Malysheva et al, 2001). Strong overall suppression of ATP-expensive protein synthesis has also been confirmed in hibernators in both in vivo and in vitro studies that monitored 14 C-leucine or 3 H-leucine incorporation into proteins (Frerichs et al, 1998;Hittel and Storey, 2002;Osborne et al, 2004).…”

Metabolic reprogramming involving glycolysis in the hibernating brown bear skeletal muscle

“…In addition, obscurin (OBSCN) has been shown to interact with Na + /K + ATPase [44], and, although its ability to phosphorylate Na + /K + ATPase has not be demonstrated in vitro, its increased levels in muscle of hibernating bears make it a possible candidate for modulating ion pump activity. Sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase (SERCA) has also been shown to be repressed, both in activity and protein levels in skeletal muscle of the long-tailed ground squirrel ( Urocitellus undulatus) during winter [45]. We found that the abundance of the three SERCA isoforms did not change in the muscle of hibernating bears, but we cannot exclude the possibility that SERCA activity could be modulated during hibernation such as by endogenous protein effectors like sarcolipin, by post-translational modifications, or in relation with the lipid composition of the sarcoplasmic reticulum membrane [46, 47].…”

Anti-apoptotic signaling as a cytoprotective mechanism in mammalian hibernation

“…Controlled suppression of both the Na + K + ATPase and the sarco(endo)plasmic reticulum Ca 2+ pump (SERCA) that returns Ca 2+ into the ER has been well-documented in multiple hypometabolic systems, including hibernators. Indeed, ground squirrels show coordinated regulation of SERCA and other Ca 2+ -related proteins in the ER (Malysheva et al, 2001). Hence, we can propose that BI-1 may be involved not just in anti-apoptosis action at the mitochondria but also in the regulation of Ca 2+ fluxes in the ER, potentially contributing to the temperature-dependent regulation of Ca 2+ fluxes that could otherwise cause damage to hibernator cells as their Tb changes over a wide range from 37 °C down to near 4 °C.…”