scholarly journals Autophagy up-regulation by early weaning in the liver, spleen and skeletal muscle of piglets

2011 ◽  
Vol 106 (2) ◽  
pp. 213-217 ◽  
Author(s):  
Shaojin Zhang ◽  
Xiao Li ◽  
Lei Li ◽  
Xianghua Yan

Autophagy, a catabolic process responsible for the degradation of cytosolic components and the preservation of cellular homeostasis in virtually all eukaryotic organisms, is up-regulated when nutrient supplies are limited. However, whether early weaning induces autophagy in infants is not completely clear. In the present study, we used piglets as the early-weaning model to examine the autophagic activity in different tissues in response to nutrient status. Western blot analysis demonstrated that microtubule-associated protein 1 light chain 3-II, a promising marker protein for macroautophagy, was expressed at a notably higher level at 12 and 24 h weaning treatments than without weaning treatment (P < 0·01), and that the p62 (sequestome 1; SQSTM1) expression level was significantly attenuated after weaning treatments (P < 0·01) in the liver, spleen and skeletal muscle tissues. In addition, autophagic vacuoles detected by transmission electron microscopy were dramatically accumulated in these tissues (P < 0·01). Together, these results indicate that autophagy induced by early weaning may be helpful for the physiological system, which controls the balance of energy and nutrients for basic cell functions in the piglet model.

2011 ◽  
Vol 80 (1) ◽  
pp. 119-124 ◽  
Author(s):  
Katarína Holovská ◽  
Viera Almášiová ◽  
Viera Cigánková ◽  
Peter Škrobánek

The aim of the present study was to investigate the effects of simulated microgravity (hypodynamia) on the structure of the skeletal muscle (m. gastrocnemius) in developing Japanese quail by transmission electron microscopy. Samples of muscle tissues from experimental (n = 28) and control (n = 28) birds were collected at day 7, 14, 28, 42 and 56 of age. The structure of m. gastrocnenmius was changed depending on hypodynamia length. The first extensive structural changes were found on day 14 of age. The mitochondria were enlarged and the spaces between the myofibrils were slightly extended compared to control. The sarcomeres were irregular and lipid droplets occurred in the sarcoplasm. Further developmental changes occurred on day 28 of age. Mitochondria fused into the giant mitochondria which frequently exceeded the length of one sarcomere. Moreover, at 42 days of age, beside the above mentioned changes, sarcoplasmic reticulum was dilated and the number of mitochondrial cristae was reduced. However, the structure of m. gastrocnemius on day 56 was less damaged compared to the damage observed on day 42 of age. Presented results indicate that the continuous stay of male Japanese quail under simulated microgravity has a negative impact on the structure of m. gastrocnemius, but also the ability of muscle tissue to cope with these specific conditions.


2021 ◽  
Vol 8 (1) ◽  
pp. 6
Author(s):  
Divya Gupta ◽  
Jeffrey W. Santoso ◽  
Megan L. McCain

Engineered in vitro models of skeletal muscle are essential for efficiently screening drug safety and efficacy. However, conventional culture substrates poorly replicate physical features of native muscle and do not support long-term culture, which limits tissue maturity. Micromolded gelatin hydrogels cross-linked with microbial transglutaminase (gelatin-MTG hydrogels) have previously been shown to induce C21C2 myotube alignment and improve culture longevity. However, several properties of gelatin-MTG hydrogels have not been systematically characterized, such as changes in elastic modulus during incubation in culture-like conditions and their ability to support sarcomere maturation. In this study, various gelatin-MTG hydrogels were fabricated and incubated in ambient or culture-like conditions. Elastic modulus, mass, and transmittance were measured over a one- or two-week period. Compared to hydrogels in phosphate buffered saline (PBS) or ambient air, hydrogels in Dulbecco’s Modified Eagle Medium (DMEM) and 5% CO2 demonstrated the most stable elastic modulus. A subset of gelatin-MTG hydrogels was micromolded and seeded with C2C12 or primary chick myoblasts, which aligned and fused into multinucleated myotubes with relatively mature sarcomeres. These data are important for fabricating gelatin-MTG hydrogels with predictable and stable mechanical properties and highlight their advantages as culture substrates for engineering relatively mature and stable muscle tissues.


2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Mija Marinković ◽  
Matilda Šprung ◽  
Maja Buljubašić ◽  
Ivana Novak

In the last two decades, accumulating evidence pointed to the importance of autophagy in various human diseases. As an essential evolutionary catabolic process of cytoplasmatic component digestion, it is generally believed that modulating autophagic activity, through targeting specific regulatory actors in the core autophagy machinery, may impact disease processes. Both autophagy upregulation and downregulation have been found in cancers, suggesting its dual oncogenic and tumor suppressor properties during malignant transformation. Identification of the key autophagy targets is essential for the development of new therapeutic agents. Despite this great potential, no therapies are currently available that specifically focus on autophagy modulation. Although drugs like rapamycin, chloroquine, hydroxychloroquine, and others act as autophagy modulators, they were not originally developed for this purpose. Thus, autophagy may represent a new and promising pharmacologic target for future drug development and therapeutic applications in human diseases. Here, we summarize our current knowledge in regard to the interplay between autophagy and malignancy in the most significant tumor types: pancreatic, breast, hepatocellular, colorectal, and lung cancer, which have been studied in respect to autophagy manipulation as a promising therapeutic strategy. Finally, we present an overview of the most recent advances in therapeutic strategies involving autophagy modulators in cancer.


Lab on a Chip ◽  
2017 ◽  
Vol 17 (20) ◽  
pp. 3447-3461 ◽  
Author(s):  
Gaurav Agrawal ◽  
Aereas Aung ◽  
Shyni Varghese

We introduce a microfluidic platform in which we culture three-dimensional skeletal muscle tissues, while evaluating tissue formation and toxin-induced muscle injury.


Author(s):  
MC Sharma ◽  
C Sarkar ◽  
NR Jagannathan ◽  
Uma Sharma ◽  
S Atri

2019 ◽  
Vol 13 (3) ◽  
Author(s):  
Jack R. T. Darby ◽  
Alexandra Sorvina ◽  
Christie A. Bader ◽  
Mitchell C. Lock ◽  
Jia Yin Soo ◽  
...  

2019 ◽  
Vol 43 (1) ◽  
pp. 69-75
Author(s):  
Scott Medler

Frogs are routinely used in physiology teaching laboratories to demonstrate important physiological processes. There have been recent directives that promote the use of the anesthetic MS-222 (tricaine methanesulfonate), rather than lowering body temperature with a cold water bath to prepare reptiles and amphibians for physiological experiments or euthanasia. Indeed, the most recent edition of the American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals proclaims that chilling in water is not an appropriate method and advocates for the usage of MS-222 or other anesthetics. However, prominent researchers have responded to this position by highlighting evidence that cooling ectothermic vertebrates is, in fact, an effective and appropriate method. Furthermore, MS-222 is a known voltage-gated Na+ channel blocker, and this anesthetic’s impact on the physiology of excitable tissues suggests that its use might be incompatible with experiments on nerve and muscle tissues. In the present study, I examined the effects of MS-222 at a concentration of 1.5 g/l on nerve, skeletal muscle, and cardiac muscle physiology of frogs. I found that immersion of frogs in this anesthetic blocked basic nerve and muscle physiology, making the frogs unsuitable for laboratory experiments. Applying MS-222 directly to the sciatic nerve dramatically blocked normal excitation-contraction coupling in skeletal muscle preparations, and direct application to the heart caused the organs to stop contracting. Based on these results, I conclude that MS-222 at the concentration studied may be incompatible with physiological preparations that rely on electrically excitable tissues for their normal function. Physiology educators who must use MS-222 with frogs should empirically determine an appropriate dosage and recovery time before using the anesthetic in the teaching laboratory.


2019 ◽  
Vol 151 (9) ◽  
pp. 1146-1155 ◽  
Author(s):  
Judith A. Heiny ◽  
Stephen C. Cannon ◽  
Marino DiFranco

Ion movements across biological membranes, driven by electrochemical gradients or active transport mechanisms, control essential cell functions. Membrane ion movements can manifest as electrogenic currents or electroneutral fluxes, and either process can alter the extracellular and/or intracellular concentration of the transported ions. Classic electrophysiological methods allow accurate measurement of membrane ion movements when the transport mechanism produces a net ionic current; however, they cannot directly measure electroneutral fluxes and do not detect any accompanying change in intracellular ion concentrations. Here, we developed a method for simultaneously measuring ion movements and the accompanying dynamic changes in intracellular ion concentrations in intact skeletal muscle fibers under voltage or current clamp in real time. The method combines a two-microelectrode voltage clamp with ion-selective and reference microelectrodes (four-electrode system). We validate the electrical stability of the system and the viability of the preparation for periods of ∼1 h. We demonstrate the power of this method with measurements of intracellular Cl−, H+, and Na+ to show (a) voltage-dependent redistribution of Cl− ions; (b) intracellular pH changes induced by changes in extracellular pCO2; and (c) electroneutral and electrogenic Na+ movements controlled by the Na,K-ATPase. The method is useful for studying a range of transport mechanisms in many cell types, particularly when the transmembrane ion movements are electrically silent and/or when the transport activity measurably changes the intracellular activity of a transported ion.


2019 ◽  
Vol 20 (20) ◽  
pp. 5130 ◽  
Author(s):  
Shunshun Han ◽  
Can Cui ◽  
Haorong He ◽  
Xiaoxu Shen ◽  
Yuqi Chen ◽  
...  

Myoferlin (MyoF), which is a calcium/phospholipid-binding protein expressed in cardiac and muscle tissues, belongs to the ferlin family. While MyoF promotes myoblast differentiation, the underlying mechanisms remain poorly understood. Here, we found that MyoF not only promotes C2C12 myoblast differentiation, but also inhibits muscle atrophy and autophagy. In the present study, we found that myoblasts fail to develop into mature myotubes due to defective differentiation in the absence of MyoF. Meanwhile, MyoF regulates the expression of atrophy-related genes (Atrogin-1 and MuRF1) to rescue muscle atrophy. Furthermore, MyoF interacts with Dishevelled-2 (Dvl-2) to activate canonical Wnt signaling. MyoF facilitates Dvl-2 ubiquitination resistance by reducing LC3-labeled Dvl-2 levels and antagonizing the autophagy system. In conclusion, we found that MyoF plays an important role in myoblast differentiation during skeletal muscle atrophy. At the molecular level, MyoF protects Dvl-2 against autophagy-mediated degradation, thus promoting activation of the Wnt/β-catenin signaling pathway. Together, our findings suggest that MyoF, through stabilizing Dvl-2 and preventing autophagy, regulates Wnt/β-catenin signaling-mediated skeletal muscle development.


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