"Autophagic flux" in normal mouse tissues: Focus on endogenous LC3A processing

Zois, Christos E.; Giatromanolaki, Alexandra; Sivridis, Efthimios; Papaiakovou, Marina; Kainulainen, Heikki; Koukourakis, Michael I.

doi:10.4161/auto.7.11.16664

Cited by 59 publications

(50 citation statements)

References 21 publications

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“…Autophagy is the major cellular route for the degradation of long-lived proteins and cytoplasmic organelles (20,45,61). After the first 2 wk of myostatin and activin blocking, concurrently with the decreased running after sActRIIB-Fc administration, we also observed a decreased level of LC3 II protein, a marker of autophagy (44).…”

Section: Discussionmentioning

confidence: 56%

Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice

Hulmi

Oliveira

Silvennoinen

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Hulmi JJ, Oliveira BM, Silvennoinen M, Hoogaars WM, Pasternack A, Kainulainen H, Ritvos O. Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice. Am J Physiol Endocrinol Metab 305: E171-E182, 2013. First published May 14, 2013 doi:10.1152/ajpendo.00065.2013.-The importance of adequate levels of muscle size and function and physical activity is widely recognized. Myostatin/activin blocking increases skeletal muscle mass but may decrease muscle oxidative capacity and can thus be hypothesized to affect voluntary physical activity. Soluble activin receptor IIB (sActRIIB-Fc) was produced to block myostatin/activins. Modestly dystrophic mdx mice were injected with sActRIIB-Fc or PBS with or without voluntary wheel running exercise for 7 wk. Healthy mice served as controls. Running for 7 wk attenuated the sActRIIB-Fc-induced increase in body mass by decreasing fat mass. Running also enhanced/restored the markers of muscle oxidative capacity and autophagy in mdx mice to or above the levels of healthy mice. Voluntary running activity was decreased by sActRIIB-Fc during the first 3-4 wk correlating with increased body mass. Home cage physical activity of mice, quantified from the force plate signal, was decreased by sActRIIB-Fc the whole 7-wk treatment in sedentary mice. To understand what happens during the first weeks after sActRIIB-Fc administration, when mice are less active, healthy mice were injected with sActRIIB-Fc or PBS for 2 wk. During the sActRIIB-Fc-induced rapid 2-wk muscle growth period, oxidative capacity and autophagy were reduced, which may possibly explain the decreased running activity. These results show that increased muscle size and decreased markers of oxidative capacity and autophagy during the first weeks of myostatin/activin blocking are associated with decreased voluntary activity levels. Voluntary exercise in dystrophic mice enhances the markers of oxidative capacity and autophagy to or above the levels of healthy mice. myostatin; activin receptor IIB; exercise; skeletal muscle; hypertrophy ADEQUATE SIZE AND FUNCTION of skeletal muscle are of paramount importance for health (3,11,49,58,60). Duchenne muscular dystrophy (DMD) is a disease characterized by progressive wasting of skeletal muscle (28). Restoration of dystrophin expression in all muscles of the body is difficult, and the effectiveness of such treatment likely depends on the muscle quality of DMD patients. Therefore, approaches aimed at stimulation of muscle growth and function are being developed that may complement dystrophin restoration approaches.Type IIB activin receptors (ActRIIB) are expressed in skeletal muscle (21, 37) and mediate the signaling of myostatin and activins (37, 59). Myostatin and activin are efficiently blocked by systemic injection of a soluble ligand binding domain of ActRIIB fused to the Fc domain of IgG (sActRIIB-Fc) (38). sActRIIB-Fc rapidly increases muscle mass and function and alleviates the disease phenotype...

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Section: Discussionmentioning

confidence: 56%

Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice

Hulmi

Oliveira

Silvennoinen

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

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“…Autophagy is an evolutionarily-conserved catabolic degradation process utilised by eukaryotic cells and tissues in response to environmental stresses such as starvation and disease (Sandri 2010, Choi et al, 2013 and it also plays important roles in development and differentiation (Mizushima and Komatsu 2011, Zois et al, 2011, Murrow and Debnath 2013. The fact that autophagy involves degradation by the autolysosome, which is formed by fusion of an autophagasome and a lysosome, suggests that NAADP signalling and TPCs might be involved in this process.…”

Section: Role Of Naadp and Tpcs In Autophagymentioning

confidence: 99%

Calcium signals regulated by NAADP and two-pore channels - their role in development, differentiation and cancer

Parrington¹,

Lear²,

Hachem³

2015

Int. J. Dev. Biol.

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“…Given that LC3 is expressed as different isoforms in mammalian cells 32 and that many commercialized LC3-antibodies are not isoform specific, 33 we first tested whether the LC3 antibodies used in this study could bind to recombinant LC3A and/or LC3B. Both proteins are currently the best-studied in situ markers for autophagy.…”

Section: Gfp-lc3mentioning

confidence: 99%

Immunohistochemical analysis of macroautophagy

et al. 2013

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T ransmission electron microscopy (TEM) is an indispensable standard method to monitor macroautophagy in tissue samples. Because TEM is time consuming and not suitable for daily routine, many groups try to identify macroautophagy in tissue by conventional immunohistochemistry. The aim of the present study was to evaluate whether immunohistochemical assessment of macroautophagy-related marker proteins such as LC3, ATG5, CTSD/cathepsin D, BECN1/Beclin 1 or SQSTM1/p62 is feasible and autophagy-specific. For this purpose, livers from starved mice were used as a model because hepatocytes are highly sensitive to autophagy induction. ATG7-deficient mouse livers served as negative control. Our findings indicate that unambiguous immunodetection of LC3 in paraffin-embedded tissue specimens was hampered due to low in situ levels of this protein. Maximum sensitivity could only be obtained using high-quality, isoform-specific antibodies, such as antibody 5F10, in combination with Envision+ signal amplification. Moreover, LC3 stains were optimal in neutral-buffered formalin-fixed tissue, immersed in citrate buffer during antigen retrieval. However, even when using this methodology, LC3 monitoring required overexpression of the protein, e.g., in GFP-LC3 transgenic mice. This was not only the case for the liver but also for other organs including heart, skeletal muscle, kidney and gut.

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"Autophagic flux" in normal mouse tissues: Focus on endogenous LC3A processing

Cited by 59 publications

References 21 publications

Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice

Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice

Calcium signals regulated by NAADP and two-pore channels - their role in development, differentiation and cancer

Immunohistochemical analysis of macroautophagy

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