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3.
Summary In the rabbit testicular ornithine decarboxylase activity and androgen content as well as serum androgens were increased 4 h after the injection of HCG. D,L- a-difluoromethylornithine ( a-DFMO) alone or together with HCG inhibited enzyme activity although testicular and serum androgens were significantly increased after a-DFMO and HCG. These data suggest that ODC activity is not required for testicular androgen production.This work was supported by the Medical Research Council of Canada, MT 4192. 相似文献
5.
Myostatin, a member of the transforming growth factor-β superfamily, is a potent negative regulator of skeletal muscle growth and is conserved in many species, from rodents to humans. Myostatin inactivation can induce skeletal muscle hypertrophy, while its overexpression or systemic administration causes muscle atrophy. As it represents a potential target for stimulating muscle growth and/or preventing muscle wasting, myostatin regulation and functions in the control of muscle mass have been extensively studied. A wealth of data strongly suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression. Moreover, myostatin plays a central role in integrating/mediating anabolic and catabolic responses. Myostatin negatively regulates the activity of the Akt pathway, which promotes protein synthesis, and increases the activity of the ubiquitin–proteasome system to induce atrophy. Several new studies have brought new information on how myostatin may affect both ribosomal biogenesis and translation efficiency of specific mRNA subclasses. In addition, although myostatin has been identified as a modulator of the major catabolic pathways, including the ubiquitin–proteasome and the autophagy–lysosome systems, the underlying mechanisms are only partially understood. The goal of this review is to highlight outstanding questions about myostatin-mediated regulation of the anabolic and catabolic signaling pathways in skeletal muscle. Particular emphasis has been placed on (1) the cross-regulation between myostatin, the growth-promoting pathways and the proteolytic systems; (2) how myostatin inhibition leads to muscle hypertrophy; and (3) the regulation of translation by myostatin. 相似文献
7.
Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) antagonized the effect of exogenous androgens on the ventral prostate (VP) in castrated rats as well as the effect of endogenous androgens in intact rats. FA, however, had no effect on the seminal vesicles (SV) and levator ani muscle (LAM), nor oestrogenic effect in female rats and mice. FA did not antagonize the receptor binding of testosterone nor inhibit the conversion of testosterone into 5 alpha-dihydrotestosterone (DHT). 相似文献
8.
We recently demonstrated that skeletal muscle differentiation induced by sphingosine 1-phosphate (S1P) requires gap junctions
and transient receptor potential canonical 1 (TRPC1) channels. Here, we searched for the signaling pathway linking the channel
activity with Cx43 expression/function, investigating the involvement of the Ca 2+-sensitive protease, m-calpain, and its targets in S1P-induced C2C12 myoblast differentiation. Gene silencing and pharmacological inhibition of
TRPC1 significantly reduced Cx43 up-regulation and Cx43/cytoskeletal interaction elicited by S1P. TRPC1-dependent functions
were also required for the transient increase of m-calpain activity/expression and the subsequent decrease of PKCα levels. Remarkably, Cx43 expression in S1P-treated myoblasts
was reduced by m-calpain-siRNA and enhanced by pharmacological inhibition of classical PKCs, stressing the relevance for calpain/PKCα axis
in Cx43 protein remodeling. The contribution of this pathway in myogenesis was also investigated. In conclusion, these findings
provide novel mechanisms by which S1P regulates myoblast differentiation and offer interesting therapeutic options to improve
skeletal muscle regeneration. 相似文献
12.
The remodeling of the mitochondrial network is a critical process in maintaining cellular homeostasis and is intimately related to mitochondrial function. The interplay between the formation of new mitochondria (biogenesis) and the removal of damaged mitochondria (mitophagy) provide a means for the repopulation of the mitochondrial network. Additionally, mitochondrial fission and fusion serve as a bridge between biogenesis and mitophagy. In recent years, the importance of these processes has been characterised in multiple tissue- and cell-types, and under various conditions. In skeletal muscle, the robust remodeling of the mitochondrial network is observed, particularly after injury where large portions of the tissue/cell structures are damaged. The significance of mitochondrial remodeling in regulating skeletal muscle regeneration has been widely studied, with alterations in mitochondrial remodeling processes leading to incomplete regeneration and impaired skeletal muscle function. Needless to say, important questions related to mitochondrial remodeling and skeletal muscle regeneration still remain unanswered and require further investigation. Therefore, this review will discuss the known molecular mechanisms of mitochondrial network remodeling, as well as integrate these mechanisms and discuss their relevance in myogenesis and regenerating skeletal muscle. 相似文献
13.
Summary Isolated human term placenta mitochondria catalyse oxidation of external NADH in the presence of cytochrome c. This reaction is insensitive to the respiratory chain inhibitors such as rotenone and antimycin A, and is not coupled to phosphorylation. Comparison of the effect of Mg ++ ion on NADH plus cytochrome c oxidation by human term placental, human skeletal muscle and rat skeletal mitochondria showed that Mg ++ ion exerts an inhibitory effect in the case of human mitochondria and a stimulatory effect in the case of rat skeletal muscle mitochondria.This work has been supported by a grant from Ministry of Higher Education Science and Technology within the project No. 01.02. 相似文献
15.
Summary Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) antagonized the effect of exogenous androgens on the ventral prostate (VP) in castrated rats as well as the effect of endogenous androgens in intact rats. FA, however, had no effect on the seminal vesicles (SV) and levator ani muscle (LAM), nor oestrogenic effect in female rats and mice. FA did not antagonize the receptor binding of testosterone nor inhibit the conversion of testosterone into 5-dihydrotestosterone (DHT).Supported in part by the project fund (grant 53-403) of Kawasaki Medical School.The authors would like to thank the Central Laboratory, Sankyo Pharmaceutical Co., Tokyo, for supplying 19-nortestosterone-17-ferulate. 相似文献
16.
Muscle satellite cells are resistant to cytotoxic agents, and they express several genes that confer resistance to stress, thus allowing efficient dystrophic muscle regeneration after transplantation. However, once they are activated, this capacity to resist to aggressive agents is diminished resulting in massive death of transplanted cells. Although cell immaturity represents a survival advantage, the signalling pathways involved in the control of the immature state remain to be explored. Here, we show that incubation of human myoblasts with retinoic acid impairs skeletal muscle differentiation through activation of the retinoic-acid receptor family of nuclear receptor. Conversely, pharmacologic or genetic inactivation of endogenous retinoic-acid receptors improved myoblast differentiation. Retinoic acid inhibits the expression of early and late muscle differentiation markers and enhances the expression of myogenic specification genes, such as PAX7 and PAX3. These results suggest that the retinoic-acid-signalling pathway might maintain myoblasts in an undifferentiated/immature stage. To determine the relevance of these observations, we characterised the retinoic-acid-signalling pathways in freshly isolated satellite cells in mice and in siMYOD immature human myoblasts. Our analysis reveals that the immature state of muscle progenitors is correlated with high expression of several genes of the retinoic-acid-signalling pathway both in mice and in human. Taken together, our data provide evidences for an important role of the retinoic-acid-signalling pathway in the regulation of the immature state of muscle progenitors. 相似文献
17.
MicroRNAs (miRNAs) are a recently discovered family of small regulatory molecules that function by modulating protein production.
There are approximately 500 known mammalian miRNA genes, and each miRNA may regulate hundreds of different protein-coding
genes. Mature miRNAs bind to target mRNAs in a protein complex known as the miRNA-induced silencing complex (miRISC), sometimes
referred to as the miRNP (miRNA-containing ribonucleoprotein particles), where mRNA translation is inhibited or mRNA is degraded.
These actions of miRNAs have been shown to regulate several developmental and physiological processes including stem cell
differentiation, haematopoiesis, cardiac and skeletal muscle development, neurogenesis, insulin secretion, cholesterol metabolism
and the immune response. Furthermore, aberrant expression has been implicated in a number of diseases including cancer and
heart disease. The role of miRNAs in these developmental, physiological and pathological processes will be reviewed.
Received 3 August 2007; received after revision 3 October 2007; accepted 5 October 2007 相似文献
18.
Summary An enteric neural receptor for serotonin (5-HT) has been characterized. This receptor was assayed, using 3H-5-HT as a radiologand, by rapid filtration of isolated enteric membranes and by radioautography. In addition, intracellular recordings were made from ganglion cells of the myenteric plexus. High affinity, saturable, reversible, and specific binding of 3H-5-HT was demonstrated both to membranes of the dissected longitudinal muscle with adherent myenteric plexus and the mucosa-submucosa. Radioautographs showed these 3H-5-HT binding sites to be in myenteric ganglia and in a broad unresolved band at the mucosal-submucosal interface. Antagonists active at receptors for other neurotransmitters than 5-HT, at either of the two known types of CNS 5-HT receptor, and at 5-HT uptake sites on serotonergic neurons failed to inhibit binding of 3H-5-HT. The structural requirements of analogues for binding to the enteric 5-HT receptor matched the known pharmacology of M or neural 5-HT receptors. A novel 5-HT antagonist was found. This compound, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), antagonized the action of 5-HT on type II/AH cells of the myenteric plexus but did not affect the release or actions of acetylcholine (nicotinic or muscarinic) or substance P. 5-HTP-DP was also an equally potent displacer of 3H-5-HT from its binding sites on enteric membranes. It is concluded that the sites responsible for specific binding of 3H-5-HT are enteric M or neural 5-HT receptors. These receptors differ from those now known to be present in the CNS. 相似文献
19.
Summary Changes in the specific activity of alkaline phosphatase in the normal and denervated skeletal muscle have been studied both histochemically as well as biochemically for a maximum period of 8 weeks of its postnatal development. In the normal muscle, a heterogenous population of fibres with respect to the enzyme distribution is observed. Relatively higher levels of enzyme in the denervated muscle and also the proliferation of extrafibrillar connective tissue in the diseased muscle show its specific association with the lytic processes. 相似文献
20.
Summary A calmodulin stimulated Ca 2+-transport ATPase which has many of the characteristics of the erythrocyte type Ca 2+-transport ATPase has been purified from smooth muscle. In particular, the effect of calmodulin on these transport enzymes is mimiced by partial proteolysis and antibodies against erythrocyte Ca 2+-transport ATPase also bind to the smooth muscle (Ca 2++Mg 2+)ATPase. A correlation between the distribution of the calmodulin stimulated (Ca 2++Mg 2+)ATPase and (Na ++K +)ATPase activities in smooth muscle membranes separated by density gradient centrifugation suggests a plasmalemmal distribution of this (Ca 2++Mg 2+)ATPase. A phosphoprotein intermediate in smooth muscle which strongly resembles the corresponding phosphoprotein in sarcoplasmic reticulum of skeletal muscle may indicate the presence in smooth muscle of a similar type of Ca 2+-transport ATPase. 相似文献
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