Corrigendum to "Superoxide Anion Production and Bioenergetic Profile in Young and Elderly Human Primary Myoblasts".

[This corrects the article DOI: 10.1155/2018/2615372.].

Superoxide Anion Production and Bioenergetic Profile in Young and Elderly Human Primary Myoblasts.

Sarcopenia is the age-related loss of skeletal muscle mass, strength, and function. It is associated with regenerative difficulties by satellite cells, adult muscle stem cells, and alteration of oxidative management, mainly the increase in superoxide anions (O2•-). We aimed to investigate the relation between regenerative deficit in elderly and increase in O2•- production along with mitochondrial alterations. Myoblasts and myotubes from skeletal muscle of young and elderly healthy subjects (27.8 ± 6 and 72.4 ± 6.5 years old) were measured: (1) superoxide dismutase activity and protein content, (2) mitochondrial O2•- production levels, (3) O2•- production variability, and (4) mitochondrial bioenergetic profile. Compared to young myoblasts, elderly myoblasts displayed decreased SOD2 protein expression, elevated mitochondrial O2•- baseline levels, and decreased oxidative phosphorylation and glycolysis. Additionally, elderly versus young myotubes showed elevated mitochondrial O2•- levels when stressed with N-acetyl cysteine or high glucose and higher glycolysis despite showing comparable oxidative phosphorylation levels. Altogether, the elderly may have less metabolic plasticity due to the impaired mitochondrial function caused by O2•-. However, the increased energy demand related to the differentiation process appears to activate compensatory mechanisms for the partial mitochondrial dysfunction.

Myomir dysregulation and reactive oxygen species in aged human satellite cells.

Satellite cells that reside on the myofibre surface are crucial for the muscle homeostasis and regeneration. Aging goes along with a less effective regeneration of skeletal muscle tissue mainly due to the decreased myogenic capability of satellite cells. This phenomenon impedes proper maintenance and contributes to the age-associated decline in muscle mass, known as sarcopenia. The myogenic potential impairment does not depend on a reduced myogenic cell number, but mainly on their difficulty to complete a differentiation program. The unbalanced production of reactive oxygen species in elderly people could be responsible for skeletal muscle impairments. microRNAs are conserved post-transcriptional regulators implicated in numerous biological processes including adult myogenesis. Here, we measure the ROS level and analyze myomiR (miR-1, miR-133b and miR-206) expression in human myogenic precursors obtained from Vastus lateralis of elderly and young subjects to provide the molecular signature responsible for the differentiation impairment of elderly activated satellite cells.

Myogenic potential of canine craniofacial satellite cells.

The skeletal fibers have different embryological origin; the extraocular and jaw-closer muscles develop from prechordal mesoderm while the limb and trunk muscles from somites. These different origins characterize also the adult muscle stem cells, known as satellite cells (SCs) and responsible for the fiber growth and regeneration. The physiological properties of presomitic SCs and their epigenetics are poorly studied despite their peculiar characteristics to preserve muscle integrity during chronic muscle degeneration. Here, we isolated SCs from canine somitic [somite-derived muscle (SDM): vastus lateralis, rectus abdominis, gluteus superficialis, biceps femoris, psoas] and presomitic [pre-somite-derived muscle (PSDM): lateral rectus, temporalis, and retractor bulbi] muscles as myogenic progenitor cells from young and old animals. In addition, SDM and PSDM-SCs were obtained also from golden retrievers affected by muscular dystrophy (GRMD). We characterized the lifespan, the myogenic potential and functions, and oxidative stress of both somitic and presomitic SCs with the aim to reveal differences with aging and between healthy and dystrophic animals. The different proliferation rate was consistent with higher telomerase activity in PSDM-SCs compared to SDM-SCs, although restricted at early passages. SDM-SCs express early (Pax7, MyoD) and late (myosin heavy chain, myogenin) myogenic markers differently from PSDM-SCs resulting in a more efficient and faster cell differentiation. Taken together, our results showed that PSDM-SCs elicit a stronger stem cell phenotype compared to SDM ones. Finally, myomiR expression profile reveals a unique epigenetic signature in GRMD SCs and miR-206, highly expressed in dystrophic SCs, seems to play a critical role in muscle degeneration. Thus, miR-206 could represent a potential target for novel therapeutic approaches.

Extracellular GTP is a potent water-transport regulator via aquaporin 5 plasma-membrane insertion in M1-CCD epithelial cortical collecting duct cells.

BACKGROUND/AIMS: Extracellular GTP is able to modulate some specific functions in neuron, glia and muscle cell models as it has been demonstrated over the last two decades. In fact, extracellular GTP binds its specific plasma membrane binding sites and induces signal transduction via [Ca(2+)]i increase. We demonstrate, for the first time, that extracellular GTP is able to modulate cell swelling in M1-CCD cortical collecting duct epithelial cells via upregulation of aquaporin 5 (AQP5) expression. METHODS: We used videoimaging, immunocitochemistry, flow cytometry, confocal techniques, Western blotting and RT-PCR for protein and gene expression analysis, respectively. RESULTS: We demonstrate that AQP5 mRNA is up-regulated 7 h after the GTP exposure in the cell culture medium, and its protein level is increased after 12-24 h. We show that AQP5 is targeted to the plasma membrane of M1-CCD cells, where it facilitates cell swelling, and that the GTP-dependent AQP5 up-regulation occurs via [Ca(2+)]i increase. Indeed, GTP induces both oscillating and transient [Ca(2+)]i increase, and specifically the oscillating kinetic appears to be responsible for blocking cell cycle in the S-phase while the [Ca(2+)]i influx, with whatever kinetic, seems to be responsible for inducing AQP5 expression. CONCLUSION: The role of GTP as a regulator of AQP5-mediated water transport in renal cells is of great importance in the physiology of renal epithelia, due to its possible physiopathological implications. GTP-dependent AQP5 expression could act as osmosensor. In addition, the data presented here suggest that GTP might play the same role in other tissues where rapid water transport is required for cell volume regulation and maintenance of the homeostasis.

A glutathione derivative with chelating and in vitro neuroprotective activities: synthesis, physicochemical properties, and biological evaluation.

Metal-ion dysregulation and oxidative stress have been linked to the progressive neurological decline associated with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Herein we report the synthesis and chelating, antioxidant, and in vitro neuroprotective activities of a novel derivative of glutathione, GS(HQ)H, endowed with an 8-hydroxyquinoline group as a metal-chelating moiety. In vitro results showed that GS(HQ)H may be stable enough to be absorbed unmodified and arrive intact to the blood-brain barrier, that it may be able to remove Cu(II) and Zn(II) from the Aß peptide without causing any copper or zinc depletion in vivo, and that it protects SHSY-5Y human neuroblastoma cells against H2 O2 - and 6-OHDA-induced damage. Together, these findings suggest that GS(HQ)H could be a potential neuroprotective agent for the treatment of neurodegenerative diseases in which a lack of metal homeostasis has been reported as a key factor.

(R)-α-lipoyl-glycyl-L-prolyl-L-glutamyl dimethyl ester codrug as a multifunctional agent with potential neuroprotective activities.

The (R)-α-lipoyl-glycyl-L-prolyl-L-glutamyl dimethyl ester codrug (LA-GPE, 1) was synthesized as a new multifunctional drug candidate with antioxidant and neuroprotective properties for the treatment of neurodegenerative diseases. Physicochemical properties, chemical and enzymatic stabilities were evaluated, along with the capacity of LA-GPE to penetrate the blood-brain barrier (BBB) according to an in vitro parallel artificial membrane permeability assay for the BBB. We also investigated the potential effectiveness of LA-GPE against the cytotoxicity induced by 6-hydroxydopamine (6-OHDA) and H2O2 on the human neuroblastoma cell line SH-SY5Y by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Our results show that codrug 1 is stable at both pH 1.3 and 7.4, exhibits good lipophilicity (log P=1.51) and a pH-dependent permeability profile. Furthermore, LA-GPE was demonstrated to be significantly neuroprotective and to act as an antioxidant against H2O2- and 6-OHDA-induced neurotoxicity in SH-SY5Y cells.