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D E Goll

Publications and source records attributed to D E Goll.

At least 19 recordsLinked to original sources
PubMed1992

Localization of the Ca(2+)-dependent proteinases and their inhibitor in normal, fasted, and denervated rat skeletal muscle.

Immunofluorescence and immunogold localization studies show that the two Ca(2+)-dependent proteinases (mu-calpain for the micromolar Ca(2+)-requiring proteinase and m-calpain for the millimolar Ca(2+)-requiring proteinase) and their protein inhibitor (calpastatin) are located exclusively intracellularly in normal rat soleus muscle. Quantitative immunogold studies indicate that binding of antibodies to both calpains and to calpastatin is approximately two times greater at the Z-disk of myofibrils than it is at the I-band or A-band regions. Mitochondria and nuclei in muscle cells contain both calpains and calpastatin at concentrations approximately one-tenth and one-fifth, respectively, of the concentration at the Z-disk, as estimated by antibody binding. Very little calpain or calpastatin was seen in the cytoplasmic intermyofibrillar spaces, and most of the calpain and calpastatin in muscle cells is associated with intracellular structures. Immunofluorescence results suggest that concentration of m-calpain but not mu-calpain or calpastatin is, in some instances, slightly higher near the intracellular surface of the plasma membrane than elsewhere in the muscle cell. Most m-calpain, however, is distributed throughout the interior of mature rat skeletal muscle cells. Denervation, or fasting and refeeding increases the concentration of the calpains and calpastatin in the muscle cell but does not change their distribution. Some mu- and m-calpain and calpastatin is found extracellularly in denervated soleus muscle or soleus muscle from fasting rats, but the extracellular calpains and calpastatin seem to originate from "leakage" of these proteins out of the cell because serum creatine kinase levels are much higher than normal in denervated or fasting rats.

Animals↗
PubMed1992

Is calpain activity regulated by membranes and autolysis or by calcium and calpastatin?

Although the Ca(2+)-dependent proteinase (calpain) system has been found in every vertebrate cell that has been examined for its presence and has been detected in Drosophila and parasites, the physiological function(s) of this system remains unclear. Calpain activity has been associated with cleavages that alter regulation of various enzyme activities, with remodeling or disassembly of the cell cytoskeleton, and with cleavages of hormone receptors. The mechanism regulating activity of the calpain system in vivo also is unknown. It has been proposed that binding of the calpains to phospholipid in a cell membrane lowers the Ca2+ concentration, [Ca2+], required for the calpains to autolyze, and that autolysis converts an inactive proenzyme into an active protease. Recent studies, however, show that the calpains bind to specific proteins and not to phospholipids, and that binding to cell membranes does not affect the [Ca2+] required for autolysis. It seems likely that calpain activity is regulated by binding of Ca2+ to specific sites on the calpain molecule, with binding to each site eliciting a response (proteolytic activity, calpastatin binding, etc.) specific for that site. Regulation must also involve an, as yet, undiscovered mechanism that increases the affinity of the Ca(2+)-binding sites for Ca2+.

Animals↗
PubMed1992

Role of the calpain system in muscle growth.

Muscle protein degradation has an important role in rate of muscle growth. It has been difficult to develop procedures for measuring rate of muscle protein degradation in living animals, and most studies have used in vitro systems and muscle strips to determine rate of protein degradation. The relationship between results obtained by using muscle strips and rate of muscle protein turnover in living animals is unclear because these strips are in negative nitrogen balance and often develop hypoxic cores. Also, rate of protein degradation is usually estimated by release of labeled amino acids, which reflects an average rate of degradation of all cellular proteins and does not distinguish between rates of degradation of different groups of proteins such as the sarcoplasmic and the myofibrillar proteins in muscle. A number of studies have suggested that the calpain system initiates turnover of myofibrillar proteins, which are the major group of proteins in striated muscle, by making specific cleavages that release thick and thin filaments from the surface of the myofibril and large polypeptide fragments from some of the other myofibrillar proteins. The calpains do not degrade myofibrillar proteins to small peptides or to amino acids, and they cause no bulk degradation of sarcoplasmic proteins. Hence, the calpains are not directly responsible for release of amino acids during muscle protein turnover. Activity of the calpains in living cells is regulated by calpastatin and Ca2+, but the nature of this regulation is still unclear.

Animals↗
PubMed1991

Binding of calpain fragments to calpastatin.

Their cDNA-derived amino acid sequences predict that the 80-kDa subunits of the micromolar and millimolar Ca(2+)-requiring forms of the Ca(2+)-dependent proteinase (mu- and m-calpain, respectively) each consist of four domains and that the 28-kDa subunit common to both mu- and m-calpain consists of two domains. The calpains were allowed to autolyze to completion, and the autolysis products were separated and were characterized by using gel permeation chromatography, calpastatin affinity chromatography, and sequence analysis. Three major fragments were obtained after autolysis of either calpain. The largest fragment (34 kDa for mu-calpain, 35 kDa for m-calpain) contains all of domain II, the catalytic domain, plus part of domain I of the 80-kDa subunit of mu- or m-calpain. This fragment does not bind to calpastatin, a competitive inhibitor of the calpains, and has no proteolytic activity in either the absence or presence of Ca2+. The second major fragment (21 kDa for mu-calpain and 22 kDa for m-calpain) contains domain IV, the calmodulin-like domain, plus approximately 50 amino acids from domain III of the 80-kDa subunit of mu- or m-calpain. The third major fragment (18 kDa) contains domain VI, the calmodulin-like domain of the 28-kDa subunit. The second and third major fragments bind to a calpastatin affinity column in the presence of Ca2+ and are eluted with EDTA. The second and third fragments are noncovalently bound, so the 80- and 28-kDa subunits of the intact calpain molecules are noncovalently bound at domains IV and VI. After separation in 1 M NaSCN, the 28-kDa subunit binds completely to calpastatin, approximately 30-40% of the 80-kDa subunit of mu-calpain binds to calpastatin, and the 80-kDa subunit of m-calpain does not bind to calpastatin in the presence of 1 mM Ca2+.

Amino Acid Sequence↗
PubMed1991

Studies of the alpha-actinin/actin interaction in the Z-disk by using calpain.

Both mu- and m-calpain (the micro- and millimolar Ca(2+)-requiring Ca(2+)-dependent proteinases) can completely remove Z-disks from skeletal muscle myofibrils and leave a space devoid of filaments in the Z-disk area. alpha-Actinin, a principal protein component of Z-disks, is removed from myofibrils by the calpains, and a 100-kDa polypeptide that comigrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with the alpha-actinin subunit is released into the supernatant. Purified calpain does not degrade purified actin or purified alpha-actinin as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by N- and C-terminal amino acid analysis of calpain-treated and untreated alpha-actinin and actin. The 100-kDa polypeptide released from myofibrils by calpain elutes identically with native alpha-actinin off DEAE-cellulose and hydroxyapatite columns and, after purification, binds to pure F-actin in the same manner that untreated, native alpha-actinin binds. Calpain-released alpha-actinin also accelerates the rate of superprecipitation of reconstituted actomyosin, a sensitive property characteristic of native alpha-actinin. Consequently, the calpains release alpha-actinin from the Z-disk of myofibrils without degrading it or without altering its ability to bind to actin. These results indicate that alpha-actinin does not simply cross-link thin filaments across the Z-disk but that at least one additional protein (or perhaps an altered actin or alpha-actinin) is involved in the alpha-actinin/actin interaction in Z-disks.

Actinin↗
PubMed1991

Comparison of the autolyzed and unautolyzed forms of mu- and m-calpain from bovine skeletal muscle.

Bovine skeletal muscle mu- and m-calpain autolyze when incubated with Ca2+. During the first 30 to 300 s, autolysis: (1) has little effect on the specific proteolytic activity of either mu- or m-calpain when assayed at 5 mM Ca2+; and (2) produces two new proteolytically active forms of calpain in addition to the original mu- and m-calpain. The four proteolytically active forms of calpain are: (1) autolyzed mu-calpain, having polypeptide subunits of 76 and 18 kDa and requiring 0.60 microM Ca2+ for half-maximal activity; (2) mu-calpain with 80- and 28-kDa subunits and requiring 7.1 microM Ca2+ for half-maximal activity; (3) autolyzed m-calpain with 78- and 18-kDa subunits and requiring 180 microM Ca2+ for half-maximal activity; and (4) m-calpain with 80- and 28-kDa subunits and requiring 1000 microM Ca2+ for half-maximal activity. All four forms of the calpains have similar pH optima (7.4 to 7.6) and almost identical circular dichroism spectra in the far ultraviolet (all four have little secondary structure with 26-30% alpha-helix and less than 10% beta-sheet structure). Autolyzed mu- and unautolyzed mu-calpain are fully activated proteolytically by Mn2+ with activity starting at 125 microM Mn2+. Autolyzed m-calpain is also activated by Mn2+ up to 80% of the maximum proteolytic activity obtained with Ca2+; Mn2+ activation begins at 320 microM Mn2+. Unautolyzed m-calpain has only 6 to 8% as much activity in the presence of Mn2+ as it does in the presence of Ca2+. Autolysis increases the axial ratios of the calpains from 3.5 to 4.6 for mu-calpain and from 3.7 to 5.0 for m-calpain (assuming 20% hydration). The estimated length of the calpain molecules increases by 13% upon autolysis from 73 to 84 A for mu-calpain and from 76 to 90 A for m-calpain (assuming 20% hydration). The autolyzed calpains elute after their unautolyzed counterparts off a DEAE-ion exchange column. Because autolyzed forms of the calpains are not found in DEAE elution profiles of cell extracts, bovine skeletal muscle cells must contain very little (less than 5% of total calpain) or none of the autolyzed form of the calpains.

Animals↗
PubMed1991

Effect of substrate on Ca2(+)-concentration required for activity of the Ca2(+)-dependent proteinases, mu- and m-calpain.

The Ca2+ concentrations required for half-maximal activity of mu- and m-calpain purified from bovine skeletal muscle were tested using four different protein substrates and three different synthetic peptide substrates. Hammersten casein, the commonly used substrate for measuring mu- and m-calpain activity, required 2.5 microM Ca2+ for half-maximal activity of mu-calpain and 290 microM Ca2+ for half-maximal activity of m-calpain. When Hammersten casein was dialyzed against 8 M urea and 10 mM EDTA to remove all endogenous Ca2+, it required 1.9 and 290 microM Ca2+ for half-maximal activity of mu- and m-calpain, respectively. Rabbit skeletal muscle myofibrils and rabbit skeletal muscle troponin required 65 microM and 24 microM Ca2+ for half-maximal activity of mu-calpain and 380 microM and 580 microM Ca2+ for half-maximal activity of m-calpain, respectively. The three synthetic substrates tested, Suc-Leu-Tyr-MCA, Boc-Leu-Thr-Arg-MCA, and Suc-Leu-Leu-Val-Tyr-MCA, required 1.6 microM to 3.7 microM Ca2+ for half-maximal activity of mu-calpain and 200 to 560 microM Ca2+ for half-maximal activity of m-calpain.

Amino Acid Sequence↗
PubMed1991

Immunolocalization of the calpains and calpastatin in human and bovine platelets.

The structure of human platelets differs from that of bovine platelets in that human platelets have a surface-connected canalicular system that bovine platelets lack. Platelets are one of the richest known sources of the calpains, and the calpains have been implicated in many of the specific cleavages of cytoskeletal and surface-receptor proteins that occur during platelet activation and aggregation. Several studies have reported that human platelets are rich in mu-calpain and contain less m-calpain, whereas bovine platelets contain principally m-calpain and almost no mu-calpain. The immunolocalization studies reported here show that calpastatin is distributed throughout the cytosol of both human and bovine platelets and that calpain is located throughout the interior of human platelets. Calpain in bovine platelets is located primarily in alpha-granules, however. Because bovine platelets contain predominantly m-calpain and because alpha-granules are translocated to the platelet surface during activation, bovine m-calpain may be responsible for the specific cleavages of platelet surface proteins such as glycoprotein Ib that occur during platelet activation and at extracellular Ca2+ concentrations high enough to activate m-calpain.

Animals↗
PubMed1990

Cross-linking and proteolysis in Ca2(+)-treated lens homogenates.

It was previously shown (Lorand et al. (1985) Biochemistry 24, 1525) that treatment of lens homogenate with Ca2+ produces two sets of changes which are catalyzed by intrinsic enzymes of the lens and which can be readily seen by alterations in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles of proteins. With the aid of differential inhibitors of the two reactions (e.g., dansylcadaverine and leupeptin) it was possible to distinguish the transglutaminase-dependent cross-linking of proteins from the proteolytic degradative phenomena. We have now shown that the proteins which are affected by the two processes can be compartmentalized differentially by centrifuging the lens homogenate after exposure to Ca2+. The dimeric and oligomeric beta-crystallin products of transglutaminase-mediated cross-linking are most clearly visible in the soluble supernatant, whereas the proteolytically susceptible proteins--possibly structural in nature, including vimentin--are predominantly present in the pellet. We have found a compound, 2-[3-(diallylamino)propionyl]benzothiophene, which, by virtue of acting as a noncompetitive inhibitor of transglutaminase as well as of calpains I and II, effectively blocked both the cross-linking seen in the supernatant and the proteolysis seen in the pellet fraction, though perhaps with somewhat different sensitivities.

Animals↗
PubMed1978

Sythesis of tropomyosin in cultures of differentiating muscle cells.

The accumulation of tropomyosin in cultures of differentiating muscle cells was quantitatively measured. Tropomyosin was isolated from cultured cells during and after myoblast fusion; both alpha- and beta-subunits were present in myotube cultures. During fusion small amounts of tropomyosin were detectable, but, as fusion approached a maximum, tropomyosin accumulation began to increase. The increased synthesis of tropomyosin after the initiation of muscle cell fusion is consistent with the increased synthesis of other proteins characteristic of muscle, including myosin.

Animals↗
PubMed1977

N- and C-terminal amino acids of purified alpha-actinin.

Highly purified bovine cardiac alpha-actinin is obtained by successive chromatography on DEAE-cellulose and hydroxyapatite of a crude fraction obtained by salting out low ionic strength extracts of bovine cardiac muscle between 0 and 30% ammonium sulfate saturation. Hydroxyapatite chromatography removes a 43 000-dalton polypeptide chain that is difficult to remove by successive DEAE-cellulose columns. Removal of all 43 000-dalton material by hydroxyapatite chromatography is accompanied by disappearance of a very small 9 to 10 S boundary in analytical ultracentrifuge diagrams of DEAE-cellulose-purified 6.2S alpha-actinin. Approximately 95% of the protein in DEAE-cellulose and hydroxyapatite-purified alpha-actinin is the 100 000-dalton alpha-actinin polypeptide as estimated by SDS-polyacrylamide gel electrophoresis. Purified bovine cardiac, porcine skeletal, chicken gizzard, and chicken breast alpha-actinins all contain leucine as the C-terminal amino acid of both polypeptide chains in the alpha-actinin molecule. Bovine cardiac and porcine skeletal alpha-actinins contain arginine as the amino acid penultimate to C-terminal leucine. None of the four different alpha-actinins studied had a N-terminal amino group available for reaction with dansyl chloride, but all four alpha-actinins contained 1.6 to 1.8 acetate residues per molecule (200 000 daltons) of alpha-actinin. It seems likely that the N-terminal amino groups of both polypeptide chains in these four alpha-actinins are acetylated. A peptide having the composition N-Ac-Asp2-Glu4 was isolated from a proteolytic digest of bovine cardiac alpha-actinin. alpha-Actinin seems to be a conserved protein molecule found in many different motile systems.

Actinin↗
PubMed1976

Some properties of purified skeletal muscle alpha-actinin.

Highly purified alpha-actinin can be made by using the low ionic strength extraction procedure previously described (Arakawa N., Robson, R. M., and Goll, D. E. (1970) Biochim. Biophys. Acta 200, 284-295) and then subjecting the crude alpha-actinin fraction obtained with this extraction procedure to successive chromatography on DEAE-cellulose and hydroxyapatite. Hydrozyapatite chromatography specifically removes a protein having a subunit molecular weight of 42,000 on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Hydroxyapatite-purified alpha-actinin sediments entirely as a 6.21 S boundary in the analytical ultracentrifuge with no trace of the small 9 to 10 S boundary seen in earlier alpha-actinin preparations purified by DEAE-cellulose chromatography. In 100 mM KCl, 20 mM Tris-acetate, pH 7.5, hydroxyapatite-purified alpha-actinin has a diffusion coefficient (D020,w) of 2.71 X 10(-7) cm2-s-1, an intrinsic viscosity of 20.6 ml-g-1, a molecular weight of 201,000 +/- 4,300 (plus or minus least squares standard error) as determined by sedimentation equilibrium, and a molecular weight of 210,000 as determined by sedimentation diffusion. In 6 M guanidine HCl, hydroxyapatite-purified alpha-actinin has a molecular weight of 106,000 +/- 6,300 as determined by sedimentation equilibrium and a molecular weight of 100,000 as determined by a calibrated 4% agarose gel permeation column. SDS-polyacrylamide gel electrophoresis gives a molecular weight of 96,000 to 100,000 for hydroxyapatite-purified alpha-actinin. Rod-shaped particles 44 X 390 to 400 A are seen in electron micrographs of negatively stained alpha-actinin. By assuming 45% hydration and a molecular weight of 206,000, dimensions of approximately 40 X 500 A can be calculated for the alpha-actinin molecule by using either s 020, w, D 020, w, intrinsic viscosity, or a calibrated 6% agarose gel permeation column. Hydroxyapatite-purified alpha-actinin has an alpha-helical content of 74% as measured by circular dichroism at 208 nm.

Actinin↗
PubMed1976

Effect of trypsin on rabbit skeletal muscle alpha-actinin.

5 min of tryptic digestion of purified rabbit skeletal alpha-actinin decreases by approximately 75% the ability of alpha-actinin to cross-link F-actin filaments as measured viscometrically at 27 degrees C, but has little effect on the sedimentation coefficient of alpha actinin at 20 degrees C or an alpha-actinin's ability to increase the Mg2+-modified ATPase activity and rate of turbidity increase of reconstituted actomyosin suspensions. Twenty to sixty min of trypsin treatment reduces the sedimentation coefficient of alpha-actinin and destroys much of alpha-actinin's ability to increase the MG2+-modified ATPase and rate of turbidity increase of reconstituted actomyosin suspensions. Therefore, the ability of alpha-actinin to increase the rate of in vitro measures of muscle contraction may not result directly from alpha-actinin's ability to cross-link F-actin filaments. Trypsin does not split alpha-actinin into large fragments as it does myosin. Previous studies have shown that 35 to 65% of total tryptic-susceptible peptide bonds in alpha-actinin are split after 60 min of incubation with trypsin and that 30% of these bonds split in 60 min are cleaved during the first 5 min in a rapid reaction. That splitting of this group of peptide bonds has little effect on the sedimentation coefficient of alpha-actinin indicates that these bonds are located in a region of the alpha-actinin molecule where noncovalent forces are strong enough to maintain conformation of the native alpha-actinin molecule even after these bonds have been split. This ostensible segregation of alpha-actinin's ability to cross-link F-actin filaments from its ability to increase rate of in vitro assays of contraction by tryptic digestion may suggest that alpha-actinin could have at least two different physiological roles: (1) to bind actin filaments to each other or to basal structures, and (2) to enhance the effectiveness of actin in supporting movement.

Actinin↗
PubMed1976

A Ca2+-activated protease possibly involved in myofibrillar protein turnover. Purification from porcine muscle.

Ca2+-activated Z-disk-removing activity in the P0-40 crude muscle extracts described by Busch et al. (Busch, W. A., Stromer, M. H., Goll, D. E., and Suzuki, A. (1972), J. Cell Biol. 52, 367) was purified from porcine skeletal muscle extracts by using five column chromatographic procedures in succession: (1) 6% agarose; (2) DEAE-cellulose; (3) Sephadex G-200; (4) DEAE-cellulose with a very shallow gradient; (5) Sephadex G-150. All Z-disk-removing activity eluted in a single peak off each column. Z-disk-removing activity always coeluted with Ca2+-activated proteolytic activity, so Z-disk-removing activity in the P0-40 crude muscle extract is due to a single Ca2+-activated protease (CAF). The five column chromatographic procedures produced a 140-fold increase in specific activity of the Ca2+-activated proteolytic enzymic activity; because preparation of the P0-40 crude CAF fraction before chromatography produced a 127-fold increase in specific activity, the entire procedure described here produces a 17 800-fold increase in specific activity of CAF. This increase in specific activity suggests that muscle contains 3.4 mug of CAF per g of muscle fresh weight; this content is in reasonably good agreement with our yields of 0.25-0.76 mug of purified CAF per g of muscle. Purified CAF migrated as a single band during polyacrylamide gel electrophoresis in pH 7.5 Tris-HC1 buffer but migrated as two bands with molecular weights of 80 000 and 30 000 during polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Densitometric scans of sodium dodecyl sulfate-polyacrylamide gels show that the 80 000- and 30 000-dalton subunits make up 85 to 90% of the protein in purified CAF preparations and that these subunits are present in equimolar ratios.

Animals↗
PubMed1976

A Ca2+-activated protease possibly involved in myofibrillar protein turnover. Partial characterization of the purified enzyme.

The purified Ca2+-activated protease (CAF) isolated from porcine skeletal muscle and capable of removing Z-disks from intact myofibrils is optimally active on either myofibril or casein substrates at pH 7.5 and in the presence of 1 mM Ca2+ and at least 2 mM 2-mercaptoethanol. No CAF activity is detected when 1 mM Mg2+, Mn2+, Ba2+, Co2+, Ni2+, and Fe2+ are added singly. When added with 1 mM Ca2+, Co2+, Cu2+, Ni2+, and Fe2+ inhibit, whereas Mg2+, Mn2+, and Ba2+ have no effect on CAF activity. CAF is irreversibly inhibited by iodoacetate but is unaffected by soybean trypsin inhibitor. S0/20,W=5.90 S, and sedimentation equilibrium molecular weight - 112 000 for purified CAF. Because purified CAF migrates as two polypeptide chains with molecular weights of 80 000 and 30 000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the CAF molecule must consist of one each of these two polypeptide chains. Approximate molecular dimensions of 38 X 220 A can be calculated for CAF from calibrated gel permeation column data or from S0/20,W and the molecular weight. Amino acid composition and physical properties of purified CAF distinguish it from the known catheptic enzymes and from other proteases found in blood or in granulocytes. Purified CAF removes Z-disks the 400-A periodicity associated with troponin in the I band and partly degrades M lines but causes no other ultrastructurally detectable effects when incubated with myofibrils. These results agree with the earlier finding that purified CAF degrades troponin, tropomyosin, and C-protein but has no effect on myosin, actin, or alpha-actinin, and suggest that CAF may have a physiological role in disassembly of intact myofibrils during metabolic turnover of myofibrillar proteins.

Amino Acids↗
PubMed1976

A Ca2+-activated protease possibly involved in myofibrillar protein turnover. Subcellular localization of the protease in porcine skeletal muscle.

A study was done to determine whether the Ca2+-activated muscle protease (CAF) that removes Z disks from myofibrils in the presence of Ca2+ is located in a sedimentable subcellular organelle. Porcine skeletal muscle cells were diced finely with a scalpel and were suspended in 0.25 M sucrose, 4 mM EDTA with a VIRTIS homogenizer. Filtration of the suspended muscle through four layers of cheesecloth removed most of the myofibrils and stromal protein. Nuclear (1,000 gavg for 15 min), mitochondrial-microsomal (50,000 gavg for 60 min), and supernatant fractions were assayed for succinic dehydrogenase, acid ribonuclease, cathepsin D, and CAF activities. Approximately 96% of total succinic dehydrogenase activity, 81% of cathepsin D activity, and 45% of acid ribonuclease activity, but only 14% of total CAF activity, were found in the nuclear and mitochondrial-microsomal fractions. Cathepsin D activity in the nuclear and mitochondrial-microsomal fractions was decreased if assays were done without prior treatment to rupture membranous structures; hence, our cell rupture and homogenization procedures preserved some intact lysosomal organelles. The results indicate that the small amount of CAF activity in the nuclear and mitochondrial-microsomal fractions was due to contamination by supernate and that CAF is not located in a membrane-bounded subcellular particle. Because CAF is active at the intracellular pH and temperature of living skeletal muscle cells and is in direct contact with the cytoplasm of muscle cells, its activity must be regulated by intracellular cellular Ca2+ concentration to prevent continuous and indiscriminate degradation of myofibrils.

Animals↗