Reduced expression of sarcalumenin and related Ca2+-regulatory proteins in aged rat skeletal muscle

Abstract

a b s t r a c tIn skeletal muscle, Ca 2+ -cycling through the sarcoplasm regulates the excitation-contraction-relaxation cycle. Since uncoupling between sarcolemmal excitation and fibre contraction may play a key role in the functional decline of aged muscle, this study has evaluated the expression levels of key Ca 2+ -handling proteins in senescent preparations using immunoblotting and confocal microscopy. Sarcalumenin, a major luminal Ca 2+ -binding protein that mediates ion shuttling in the longitudinal sarcoplasmic reticulum, was found to be greatly reduced in aged rat tibialis anterior, gastrocnemius and soleus muscle as compared to adult specimens. Minor sarcolemmal components of Ca 2+ -extrusion, such as the surface Ca 2+ -ATPase and the Na + -Ca 2+ -exchanger, were also diminished in senescent fibres. No major changes were observed for calsequestrin, sarcoplasmic reticulum Ca 2+ -ATPase and the ryanodine receptor Ca 2+ -release channel. In contrast, the age-dependent reduction in the a 1S -subunit of the dihydropryridine receptor was confirmed. Hence, this report has shown that downstream from the well-established defect in coupling between the t-tubular voltage sensor and the junctional Ca 2+ -release channel complex, additional age-related alterations exist in the expression of essential Ca 2+ -handling proteins. This may trigger abnormal luminal Ca 2+ -buffering and/or decreased plasmalemmal Ca 2+ -removal, which could exacerbate impaired signaling or disturbed intracellular ion balance in aged fibres, thereby causing contractile weakness.

DIGE analysis of rat skeletal muscle proteins using nonionic detergent phase extraction of young adult versus aged gastrocnemius tissue

“…Most physiological and histological studies of fibre aging indicate that sarcopenia is due to a multi-factorial pathology. Skeletal muscle aging is associated with a wide variety of cellular, biochemical and physiological alterations, including (i) grouped atrophying fibres, increased numbers of centrally located nuclei and variability in fibre diameter [9], (ii) metabolic alterations [43], (iii) mitochondrial disturbances and an increased susceptibility to apoptosis [44], (iv) a decreased regenerative capacity [45], (v) disturbed luminal ion binding and cycling [46], (vi) excitation-contraction uncoupling [47], (vii) oxidative stress [48], (viii) a blunted cellular stress response [49], (ix) impaired protein synthesis of myofibrillar components [50], ( (x) denervation-associated atrophy [51], (xi) an altered equilibrium of growth factors and hormones involved in fibre maintenance [52], and (xii) a severe decline in contractile efficiency [53]. Our proteomic map of alterations in protein expression in the aqueous versus detergent-extracted fractions from aged muscle agrees with the idea of complex biochemical changes in sarcopenia.…”

Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries

“…Effects of aging on the Ca 2+ signaling have been well described in skeletal muscle [44] and neurons [10,56] yet not exhaustively in VSMC [23]. Therefore, we focused our study on the channels and pumps involved in Ca 2+ signaling implicated in the regulation of vascular reactivity.…”

Drastic increase of myosin light chain MLC-2 in senescent skeletal muscle indicates fast-to-slow fibre transition in sarcopenia of old age

“…One-dimensional gel electrophoresis of the myofibrilenriched fraction was carried out with a MiniProtean III gel system (BioRad Laboratories, HemelHempstead, Herts., UK) by a standard method using 12% separation gels (O'Connell et al, 2008a). Twodimensional gel electrophoresis of the total muscle proteome and the myofibril proteome for densitometric and mass spectrometric analyses was performed as previously described in detail by our laboratory (Doran et al, 2004).…”

“…Striking histological alterations in aged skeletal muscles include an extensive variability in fibre diameter, an increased number of centrally located nuclei, grouped atrophying fibres and a higher frequency of longitudinal splitting (Edstrom et al, 2007). Previous studies into muscle aging have clearly documented the complexity of pathological changes (Faulkner et al, 2007), including a severe decline in contractile efficiency (Prochniewicz et al, 2007), mitochondrial abnormalities (Chabi et al, 2008), metabolic alterations (Vandervoort and Symons, 2001), a progressive decline in energy intake (Thomas, 2007), a drastically decreased regenerative capacity (Lorenzon et al, 2004), disturbed ion homeostasis (O'Connell et al, 2008a), uncoupling between neuronal excitation and muscle contraction (Delbono et al, 1995), decreased capillarisation (Degens, 1998), oxidative stress (Squier and Bigelow, 2000), a partially diminished cellular stress response (Kayani et al, 2008), impaired protein synthesis of myofibrillar components (Balagopal et al, 1997), increased apoptosis (Marzetti and Leeuwenburgh, 2006), denervationassociated atrophy (Carlson, 2004) and an altered equilibrium of growth factors and hormones important for the maintenance of proper muscle function (Lee et al, 2007).…”