Biomedical subjects

C A Maltin

Publications and source records attributed to C A Maltin.

At least 19 recordsLinked to original sources

PubMed2004

Moderate maternal vitamin A deficiency alters myogenic regulatory protein expression and perinatal organ growth in the rat.

Vitamin A deficiency is one of the most common dietary deficiencies in the developing world and is a major health concern where it is associated with increased risk of fetal and infant mortality and morbidity. Early studies in the rat demonstrated that, in addition to respiratory problems, neonates showed evidence of mobility problems in response to moderate vitamin A deficiency. This study investigated whether moderate deficiency of this vitamin plays a role in regulating key skeletal muscle regulatory pathways during development. Thirty female rats were fed vitamin A-moderate (VAM) or vitamin A-sufficient diets from weaning and throughout pregnancy. Fetal and neonatal hindlimb and muscle samples were collected on days 13.5, 15.5, 17.5, and 19.5 of pregnancy and 1 day following birth. Mothers fed the VAM diet had reduced retinol concentrations at all time points studied (P < 0.01), and neonates had reduced relative lung weights (P < 0.01). Fetal weight and survival did not differ between groups but neonatal survival was lower in the VAM group where neonates had increased relative heart weights (P < 0.05). Analysis of myogenic regulatory factor expression and calcineurin signaling in fetuses and neonates demonstrated decreased protein levels of myf5 [50% at 17.5 dg (P < 0.05)], myogenin [70% at birth (P < 0.001)], and myosin heavy chain fast [50% at birth (P < 0.05)] in response to moderate vitamin A deficiency. Overall, these changes suggest that vitamin A status during pregnancy may have important implications for fetal muscle development and subsequent muscle function in the offspring.

Animals↗

PubMed2003

Tetracycline-regulated secretion of human insulin in a transfected non-endocrine cell line.

Long-term constitutive secretion of insulin by implantation of ex vivo transfected cells such as fibroblasts or myoblasts or in situ by intramuscular injection of naked plasmid DNA provides a potential approach to gene therapy for diabetes mellitus. A mechanism for regulating insulin secretion will be necessary to realize the therapeutic potential of this approach. A second obstacle is the inability of non-endocrine host cells to fully process proinsulin. Therefore, alteration of the wild-type cDNA will be necessary to achieve processing of proinsulin by endogenous endoproteases within these cells. The cDNAs for beta-galactosidase (beta), human wild-type proinsulin (hppI1) and a mutated construct (hppI4), in which the dibasic PC2 and PC3 cleavage sites had been altered to form furin cleavage sites, were sub-cloned into four vectors (pCR3, pVR1012, pIRES, pTRE), including a tetracycline responsive plasmid (pTRE) that requires co-transfection with another plasmid encoding a transactivator (pTet-off) for transgene expression. Transient transfection of the COS-7 fibroblast cell line with these constructs was performed using DEAE-dextran and liposomes. Analysis of vector efficiencies revealed that pTRE/pTet-off>pIRES>pCR3>pVR1012. Further analysis demonstrated total pro/insulin secretion of 2.33 ng/10(6) cells/24 h with > or =25% processed to insulin in hppI-1.pTRE/pTet-off-transfected cells compared with 0.39 ng/10(6) cells/24 h and >70% processing in hppI-4.pTRE/pTet-off-transfected cells. In co-transfection studies with pTRE-hppI1/pTet-off and pTRE-hppI4/pTet-off constructs, pro/insulin secretion was inhibited to 65-66% and 36-38% of control (100%) in the presence of 0.01 and 0.1 microg/ml tetracycline respectively over a 24-h incubation period. Furthermore, reversal of tetracycline inhibition was demonstrated for pTRE-hppI1/pTet-off- and pTRE-hppI4/pTet-off-transfected cells. After a 48-h incubation with 1.0 microg/ml tetracycline, total pro/insulin levels were 10 and 14% compared with untreated cells respectively. On tetracycline removal, total proinsulin levels increased and were equivalent to untreated groups 72 h later. In conclusion, regulation of fully processed human insulin secretion has been achieved in a transiently transfected non-endocrine cell line.

Animals↗

PubMed2003

Slow fiber cluster pattern in pig longissimus thoracis muscle: implications for myogenesis.

Recent evidence implicates fiber type proportions as playing a role in meat eating quality, and in pigs it has been suggested that the slow oxidative fibers contribute to both juiciness and tenderness. The fiber distribution in pigs is different from that found in most other species, in which the various types of skeletal muscle fiber are distributed in a "checkerboard" pattern, because in pigs the slow oxidative fibers have a clustered distribution. The initial processes leading to fiber clustering are likely to occur during myogenesis, but the precise mechanistic aetiology of this patterning and whether the slow oxidative fiber clusters occur in a random or ordered fashion is unknown. In the present study longissimus thoracis muscle from Large White crossbred pigs was sampled at the 10th rib, 48 h postmortem. Transverse cryo-sections were cut and histochemically stained to allow the identification of the main muscle fiber types: slow oxidative, fast glycolytic, and fast oxidative glycolytic. Images of the sections were captured and analyzed using point processes and Voronoi Tesselations to examine the randomness and spatial distribution of the clusters of slow oxidative fibers found in pig longissimus thoracis muscle. The results showed that an assumption of complete spatial randomness can be rejected and that a mathematical model incorporating a minimum distance of 1.7 to 2.0 microm between cluster centers produced fiber patterns similar to those observed in the original transverse sections of the muscle. In addition, if it assumed that the central fiber in each cluster is derived from primary myoblast progenitors, these results suggest that there may be some degree of repulsion between the primary fibers during the initial stages of cluster formation. The mechanistic basis of such repulsion is not clear, but it is speculated that secreted factors, such as sonic hedgehog or myostatin may play a role.

Algorithms↗

PubMed2002

Secretion of bioactive human insulin following plasmid-mediated gene transfer to non-neuroendocrine cell lines, primary cultures and rat skeletal muscle in vivo.

The objective of these studies was to evaluate human insulin gene expression following intramuscular plasmid injection in non-diabetic rats as a potential approach to gene therapy for diabetes mellitus avoiding the need for immunosuppression. A wild-type human preproinsulin construct and a mutant construct in which PC2/PC3 sites were engineered to form furin consensus sites were evaluated in in vitro transfections of hepatocyte (HepG2) and myoblast (C2C12/L6) cell lines, primary rat myoblasts, and dermal fibroblasts. In vivo gene transfer by percutaneous plasmid injection of soleus muscle +/- prior notexin-induced myolysis was assessed in rats. In vitro transfection of non-neuroendocrine cell lines and primary cultures with wild-type human preproinsulin resulted in secretion of predominantly unprocessed proinsulin. Employing the mutant construct, there was significant processing to mature insulin (HepG2, 95%; C2C12, 75%; L6, 65%; primary myoblasts, 48%; neonatal fibroblasts, 56%; adult fibroblasts, 87%). In rats aged 5 weeks, circulating human (pro)insulin was detected from 1 to 37 days following plasmid injection and the potential of augmenting transfection efficiency by prior notexin injection was demonstrated (wild-type processing, 87%; mutant, 90%). Relative hypoglycaemia was confirmed by HbA1C (saline, 5.5%; wild type, 5.1%; mutant, 5.1% (P<0.05)). Human (pro)insulin levels and processing (wild-type, 8%; mutant, 53%) were lower in rats aged 9 months but relative hypoglycaemia was confirmed by serum glucose at 10 days (saline, 6.4 mmol/l; wild-type, 6.0 mmol/l; mutant, 5.4 mmol/l). In conclusion, prolonged constitutive systemic secretion of bioactive human (pro)insulin has been attained in non-neuroendocrine cells in vitro and in growing and mature rats following intramuscular plasmid injection.

Animals↗

PubMed2001

Elevated IGF-II mRNA and phosphorylation of 4E-BP1 and p70(S6k) in muscle showing clenbuterol-induced anabolism.

Muscle wasting affects large numbers of people, but few therapeutic approaches exist to treat and/or reverse this condition. The beta(2)-adrenoceptor agonist clenbuterol produces a muscle-specific protein anabolism in both normal and catabolic muscle and has been used to limit muscle wasting in humans. Because clenbuterol appears to interact with or mimic innervation, its effect on the expression of the neurotrophic agents insulin-like growth factor (IGF)-II and H19 and their putative pathways was examined in normal rat plantaris muscle. The results showed that the well-documented early effects of clenbuterol on protein metabolism were preceded by elevated levels of IGF-II and H19 transcripts together with increased phosphorylation of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1) and p70(S6k). By 3 days, transcript levels for IGF-II and H19 and 4E-BP1 and p70(S6k) phosphorylation had returned to control values. These novel findings indicate that clenbuterol-induced muscle anabolism is potentially mediated, at least in part, by an IGF-II-induced activation of 4E-BP1 and p70(S6k).

Adrenergic beta-Agonists↗

PubMed2001

Impact of manipulations of myogenesis in utero on the performance of adult skeletal muscle.

The possibility that early fetal programming affects health or disease status in adult life has been considered in relation to tissues such as the cardiovascular system but not with respect to skeletal muscle. Since muscle mass and function are important for life, it is pertinent to ask whether events during the development of muscle in utero can affect the performance of the tissue in later life. This review discusses the factors that influence muscle performance, outlines the current understanding of myogenesis and examines how manipulations alter myogenic outcome after birth. The performance of muscle is determined by the number, type and size of the muscle fibres, these in turn being affected by a number of factors, and the evidence indicates that the proportions of types of muscle fibre have a heritable component. The formation of muscle occurs early in embryogenesis and it appears that the major impacts on myogenesis are associated with extremes of treatment or embryo manipulations. The impact of extremes of treatment or embryo manipulations on myogenesis is seen in the secondary fibres whereas primary fibres appear to be insensitive or protected. Overall, the opportunities for manipulation of myogenesis in utero to improve adult performance are limited.

Aging↗

PubMed2000

The neurotoxicity of the venom phospholipases A(2), notexin and taipoxin.

The presynaptically active, toxic phospholipases known as notexin and taipoxin are principal components of the venom of the Australian tiger snake and the Australian taipan respectively. The inoculation of the toxins into one hind limb of rats caused, within 1 h, the depletion of transmitter from the motor nerve terminals of the soleus muscle. This was followed by the degeneration of the motor nerve terminals and of the axonal cytoskeleton. By 24 h 70% of muscle fibers were completely denervated. Regeneration and functional reinnervation were almost fully restored by 5 days, but collateral innervation was common in the regenerated muscles, and this abnormality persisted for at least 9 months. The data provide an explanation for both the severity of neuromuscular paralysis that can accompany envenoming bites by tiger snakes and taipans and the difficulty experienced by physicians in managing the envenomed subjects.

Acetylcholinesterase↗

PubMed2000

Amelioration of denervation-induced atrophy by clenbuterol is associated with increased PKC-alpha activity.

Rat soleus muscle was denervated for 3 or 7 days, and total membrane protein kinase C (PKC) activity and translocation and immunocytochemical localization of PKC isoforms were examined. Dietary administration of clenbuterol concomitant with denervation ameliorated the atrophic response and was associated with increased membrane PKC activity at both 3 (140%) and 7 (190%) days. Of the five PKC isoforms (alpha, epsilon, theta, zeta, and mu) detected in soleus muscle by Western immunoblotting, clenbuterol treatment affected only the PKC-alpha and PKC-theta forms. PKC-alpha was translocated to the membrane fraction upon denervation, and the presence of clenbuterol increased membrane-bound PKC-alpha and active PKC-alpha as assayed by Ser(657) phosphorylation. PKC-theta protein was downregulated upon denervation, and treatment with clenbuterol further decreased both cytosolic and membrane levels. Immunolocalization of PKC-theta showed differences for regulatory and catalytic domains, with the latter showing fast-fiber type specificity. The results suggest potential roles of PKC-alpha and PKC-theta in the mechanism of action of clenbuterol in alleviating denervation-induced atrophy.

Adrenergic beta-Agonists↗

PubMed2000

The effects of breed and level of nutrition on whole-body and muscle protein metabolism in pure-bred Aberdeen angus and Charolais beef steers.

Eighteen pure-bred steers (live weight 350 kg) from each of two breeds, Aberdeen Angus (AA) and Charolais (CH), were split into three equal groups (six animals each) and offered three planes of nutrition during a 20-week period. The same ration formulation was offered to all animals with amounts adjusted at 3-week intervals to give predicted average weight gains of either 1.0 kg/d (M/M group) or 1.4 kg/d (H/H group). The remaining group (M/H) were offered the same amount of ration as the M/M group until 10 weeks before slaughter when the ration was increased to H. Data on animal performance, carcass characteristics and fibre-type composition in skeletal muscle are presented elsewhere (Maltin et al. 2000; Sinclair et al. 2000). On three occasions (17, 10 and 2 weeks before slaughter) the animals were transferred to metabolism stalls for 1 week, during which total urine collection for quantification of Ntau-methylhistidine (Ntau-MeH) elimination was performed for 4 d. On the last day, animals were infused for 11 h with [2H5]phenylalanine with frequent blood sampling (to allow determination of whole-body phenylalanine flux) followed by biopsies from m. longissimus lumborum and m. vastus lateralis to determine the fractional synthesis rate of mixed muscle protein. For both breeds, the absolute amount of Ntau-MeH eliminated increased with animal age or weight (P < 0.001) and was significantly greater for CH steers, at all intake comparisons, than for AA (P < 0.001). Estimates of fractional muscle breakdown rate (FBR; calculated from Ntau-MeH elimination and based on skeletal muscle as a fixed fraction of live weight) showed an age (or weight) decline for M/M and H/H groups of both breeds (P < 0.001). FBR was greater for the H/H group (P = 0.044). The M/H group also showed a lower FBR for the first two measurement periods (both at M intake) but increased when intake was raised to H. When allowance was made for differences in lean content (calculated from fat scores and eye muscle area in carcasses at the end of period 3), there were significant differences in muscle FBR with intake (P = 0.012) but not between breed. Whole-body protein flux (WBPF; g/d) based on plasma phenylalanine kinetics increased with age or weight (P < 0.001) and was similar between breeds. The WBPF was lower for M/M compared with H/H (P < 0.001) based on either total or per kg live weight0.75. Muscle protein fractional synthesis rate (FSR) declined with age for both breeds and tended to be higher at H/H compared with M intakes (intake x period effects, P < 0.05). Changing intake from M to H caused a significant increase (P < 0.001) in FSR. The FSR values for AA were significantly greater than for CH at comparable ages (P = 0. 044). Although FSR and FBR responded to nutrition, these changes in protein metabolism were not reflected in differences in meat eating quality (Sinclair et al. 2000).

Age Factors↗

PubMed1999

Masseteric hypertrophy?: preliminary report.

We report radiological and histological investigations of a patient who presented with the masseteric hypertrophy. Sections of the patient's masseter muscles were also investigated using a series of histological techniques. The histological and morphometric analysis of the patient's masseter muscle showed numerous small fibres, which indicated that the masseteric enlargement was not the result of classic fibre hypertrophy. We suggest that the use of the term 'hypertrophy' in this condition may be misleading.

Adult↗

PubMed1999

Aberrant fetal growth and development after in vitro culture of sheep zygotes.

The effects of in vitro culture systems for sheep zygotes on subsequent fetal growth and development to day 61 and day 125 of gestation were studied. Zygotes recovered from superovulated Scottish Blackface ewes approximately 36 h after intrauterine insemination using semen from a single Suffolk sire were cultured for 5 days in (a) a granulosa cell co-culture system (co-culture); (b) synthetic oviductal fluid medium without serum (SOF-); and (c) synthetic oviductal fluid medium supplemented with human serum (SOF+). Control embryos were recovered from superovulated donor ewes at day 6 after oestrus. Embryos were transferred at day 6 to synchronous Scottish Blackface recipient ewes. In total, 146 gravid uteri were recovered, comprising 97 at day 61 (20 co-culture, 27 SOF-, 25 SOF+ and 25 control) and 49 at day 125 (13 co-culture, 8 SOF-, 6 SOF+ and 22 control) of gestation. Fetuses derived from co-cultured embryos were 14% heavier (P < 0.01) by day 61 of gestation than those derived from control embryos. Growth coefficients derived from the linear allometric equation logey = logea + b logex (where y = organ mass; x = fetal mass) were significantly greater (P < 0.05) for liver, heart, kidneys and plantaris muscle in fetuses derived from co-cultured embryos, and for liver in fetuses derived from SOF+ embryos than those for control fetuses. Fetuses derived from co-cultured embryos were 34% heavier (P < 0.001) and fetuses derived from SOF+ embryos were 18% heavier (P < 0.01) by day 125 of gestation than those derived from control embryos. Growth coefficients for liver and heart for fetuses derived from co-culture and SOF+ embryos were also significantly greater (P < 0.05) at this stage of gestation than those for control group fetuses. In contrast, allometric coefficients for these organs in fetuses derived from embryos cultured in SOF without serum supplementation were not different from those for controls. Excessive volumes of amniotic fluid (polyhydramnios) were observed in 23% of conceptuses derived from co-cultured embryos. In vitro embryo culture can significantly influence fetal growth and this study provides quantitative evidence of major shifts in the patterns of organ and tissue development.

Animals↗

PubMed1998

Fetal growth and development following temporary exposure of day 3 ovine embryos to an advanced uterine environment.

The effect of exposing Day 3 ovine embryos to an advanced uterine environment for a period of 3 days on subsequent fetal growth and development between Day 35 and Day 135 of gestation was studied. Day 3 embryos were recovered from superovulated donor ewes and transferred to synchronous final or asynchronous temporary recipients for 3 days. Embryos were recovered from these temporary recipients and transferred to Day 6 final recipients. Gravid uteri were recovered, weighed and dissected on Days 35, 45, 60, 90, 110, 125 and 135 of gestation. Fetal weight and length data were analysed by fitting non-linear Gompertz models of the form log(e) y = a - be(-ct), where y is fetal size and t is time from conception. Various terms including treatment, gestational age, embryo stage at transfer and fetal sex were fitted to this model. Fetal development was assessed by relating organ weight to fetal bodyweight using the linear allometric equation log(e) y = log(e) a + b log(e) x, where y is organ weight and x is fetal weight. Temporary exposure of Day 3 embryos to an advanced uterine environment did not increase the rate of embryo development and had no effect on fetal growth and development between Days 35 and 135 of gestation in this study. A single Gompertz model (log(e) y = 10.134 - 17.047e(-0.1733t)) explained 99.8% of the variation in fetal weight. Of terms fitted to this model only gestational age and fetal sex influenced fetal weight, with male fetuses being 5% heavier (P<0.05) than female fetuses. Fetal development was also unaffected by experimental treatment in this study. Allometric coefficients established for various fetal components agreed well with those from previously published studies.

Animals↗

PubMed1998

Temporary exposure of ovine embryos to an advanced uterine environment does not affect fetal weight but alters fetal muscle development.

Embryo transfer techniques may result in fetuses that are heavier at birth and that have been described as highly muscled. The aim of this study was to investigate myogenesis in lambs derived from embryo transfer. Embryos were transferred at Day 3 (estrus = Day 0) to a 3 days-advanced uterine environment, maintained there for 3 days, recovered, and then returned to a synchronous (Day 6) uterus; these fetuses comprised the asynchronous group. Control animals were created by synchronous embryo recovery and single transfer at Day 3. Asynchronous transfer did not affect fetal weight or curved crown-rump length between 46 and 135 days of gestation. No differences were detected between groups at Days 110-135 with respect to muscle mass or protein, RNA, and DNA content. However, total muscle fiber number was significantly increased in plantaris muscles from the asynchronous groups at Day 110 and Day 125, suggestive of prolonged hyperplasia. In addition, the levels of Myf 5 protein and the secondary-to-primary fiber ratio were altered in plantaris muscle from the asynchronous group. The growth data are in contrast to previously reported findings. The results show that fetal myogenesis can be altered by very early events in embryogenesis and suggest that any inferences made solely on the basis of fetal or muscle weight may be fallacious.

Animals↗

PubMed1998

Short-term culture of ovine embryos modifies fetal myogenesis.

Certain reproductive techniques culture embryos in vitro; however, little is known about the impact of culture on fetal growth. Coculture of day 1 ovine zygotes on a bovine granulosa cell layer to blastocysts followed by transfer to synchronous recipients increased fetal weight by 11 and 40% at days 61 and 125, respectively, compared with the transfer of in vivo-produced blastocysts. Plantaris muscle weights were increased by 40% in cultured fetuses at day 125. Examination of myogenesis in plantaris muscle showed that primary fiber number was unchanged at day 61 by culture but that primary fiber area was increased significantly by 15 and 25% at days 61 and 125, respectively; secondary fiber area was increased by 40% at day 125 by culture, and the ratio of secondary to primary fiber numbers was 18-20% greater in the cultured groups compared with the controls at days 61 and 125. The results show that coculture of preimplantation embryos may alter myogenic programming. These changes may contribute to the abnormally large muscles observed in oversize fetuses.

Animals↗

PubMed1997

Clenbuterol increases the expression of myogenin but not myoD in immobilized rat muscles.

Immobilization of one hindlimb of young rats in plantar flexion for 3 days led to changes in the plantaris muscles. These comprised a loss of muscle mass and a reduction in protein and RNA content, but no change in the transcript levels of the myogenic regulatory factors myogenin and myoD. Dietary administration of the beta-adrenoceptor agonist clenbuterol (2 mg/kg diet), which has been shown to ameliorate muscle wasting in a wide range of atrophic conditions, also limited muscle wasting in terms of weight, protein, and RNA in the immobilized plantaris muscles. In addition, drug treatment in immobilized plantaris muscles was associated with a marked increase in the steady-state levels of mRNA for myogenin (approximately 360% increase over control) but not myoD. These data provide the first evidence for independent changes in these two myogenic regulatory factors in immobilized muscle and suggest that the action of clenbuterol on these factors may depend on the mechanistic basis for the atrophic response.

Animals↗

PubMed1996

Effect of prednisone on protease activities and structural protein levels in rat muscles in vivo.

To further elucidate the biochemical mechanism by which the corticosteroid prednisone induces differential changes in muscle mass (via altered protein synthesis/degradation rates) in normal or degenerating muscle tissues, we have determined the activity of a range of proteolytic enzyme types, together with levels of muscle structural proteins, in five innervated and denervated muscle types from control and drug treated rats. In both normal and wasting muscles, the activity of many protease types was substantially down-regulated following treatment with prednisone; however, accompanying net decreases in muscle mass were observed (although the structural protein composition of muscles was unaltered following drug treatment). We conclude that whilst overall rates of protein degradation in both normal and degenerating muscle may be reduced (via protease down-regulation) following prednisone treatment, the effect of the latter in reducing protein synthesis rates must be proportionately greater (even in actively degenerating tissue). Thus, the data do not support the hypothesis that the beneficial effect of prednisone in maintaining muscle mass in pathological tissues (e.g., Duchenne muscular dystrophy (DMD)) operates principally via down-regulation of protease action/protein catabolism.

Animals↗

PubMed1995

Comparison of structural protein and proteolytic enzyme levels in degenerating and regenerating rat muscle induced by Notechis scutatus venom.

To develop a clear understanding of the biochemical mechanism of muscle degeneration and regeneration induced by a single dose of Notechis scutatus scutatus venom, we have correlated changes in the levels of a series of muscle structural proteins and proteolytic enzymes. The degradation of structural proteins post-injection fell into two broad groups; those completely degraded within 3-6 hr (e.g. C- and M-proteins, skelemin), and within 1-2 days (e.g. myosin, actin, troponin), respectively. Similarly, activation of proteases followed two general patterns; those enzymes showing substantially increased activity after 12-24 hr (lysosomal cathepsins, leucyl aminopeptidase) and those enzymes showing decreased activity after 12-24 hr, with substantially increased activity after 3-4 days (mainly cytoplasmic proteases). The data suggest that activation of cathepsins B, L and D and in particular leucyl aminopeptidase, may be responsible for the early stages of structural protein catabolism, and are thus potential therapeutic targets to prevent myonecrosis following envenomation.

Actins↗

PubMed1993

Effect of protease inhibitors and clenbuterol on the in vitro degradation of dystrophin by endogenous proteases in human skeletal muscle.

The in vitro degradation of dystrophin protein by endogenous proteases in human skeletal muscle has been investigated using a tissue homogenate assay system with subsequent protein analysis via SDS polyacrylamide electrophoresis and immunoblotting (using a monoclonal antibody to the central rod region of dystrophin). The rate of dystrophin degradation and nature of the proteolytic fragments formed at pH 5.5 and pH 7.5 (corresponding to the two major protease groups of relevance to intracellular protein catabolism) were broadly similar; incorporation of protease inhibitors in the above system suggested that Ca2+ activated proteinase and cathepsin D are principally responsible for the degradation of dystrophin at pH 7.5 and pH 5.5 respectively. The rate of dystrophin degradation at pH 7.5 was reduced by approximately 20% in the presence of 10(-5) M clenbuterol, a beta-adrenoceptor agonist with therapeutic potential in the treatment of human muscle wasting diseases.

Cathepsin D↗