Titin, a Central Mediator for Hypertrophic Signaling, Exercise-Induced Mechanosignaling and Skeletal Muscle Remodeling

Krüger, Martina; Kötter, Sebastian

doi:10.3389/fphys.2016.00076

Cited by 95 publications

(92 citation statements)

References 84 publications

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“…As expected, large increases in Titin-N fragment levels were observed in the urine of two volunteers (29-year-old male; 60.86 nmol/L, 23-year-old male; 460.71 nmol/L), collected just after running (32 km/8 hours). Since sequential processes of muscle damage, inflammatory response, hypertrophic response and sarcomerogenesis and fiber repair are induced after muscle damage2567, we analyzed the fluctuations of Titin-N fragment levels after exercise (10 km running/1 hour, 39-year-old male). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In DMD, the loss of dystrophin induces instability of the sarcolemma, particularly during contraction and, consequently, leads to a massive Ca 2+ influx into muscle fibers and the subsequent disturbance of calpain activity, resulting in the degradation of titin and sarcomere structure256. This fact suggests that titin fragments could be used for the non-invasive monitoring of muscle disease progression and the response to therapeutic treatment.…”

Section: Resultsmentioning

confidence: 99%

“…Q8WZ42)12, firstly called connectin3, is expressed in all striated muscles and is one of the largest known proteins, with a molecular weight in the range of 3.0 to 3.7 MDa. It spans a half-sarcomere from the Z-disc to the M-line, and it serves as a scaffold for sarcomerogenesis and myofibrillar assembly4.…”

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confidence: 99%

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Establishment of a highly sensitive sandwich ELISA for the N-terminal fragment of titin in urine

Maruyama

Asai

Abê

et al. 2016

Sci Rep

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Muscle damage and loss of muscle mass are triggered by immobilization, loss of appetite, dystrophies and chronic wasting diseases. In addition, physical exercise causes muscle damage. In damaged muscle, the N-terminal and C-terminal regions of titin, a giant sarcomere protein, are cleaved by calpain-3, and the resulting fragments are excreted into the urine via glomerular filtration. Therefore, we considered titin fragments as promising candidates for reliable and non-invasive biomarkers of muscle injury. Here, we established a sandwich ELISA that can measure the titin N-terminal fragment over a biologically relevant range of concentrations, including those in urine samples from older, non-ambulatory Duchenne muscular dystrophy patients and from healthy donors under everyday life conditions and after exercise. Our results indicate that the established ELISA could be a useful tool for the screening of muscular dystrophies and also for monitoring the progression of muscle disease, evaluating the efficacy of therapeutic approaches, and investigating exercise-related sarcomeric disruption and repair processes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Establishment of a highly sensitive sandwich ELISA for the N-terminal fragment of titin in urine

Maruyama

Asai

Abê

et al. 2016

Sci Rep

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“…, 2016; Krüger and Kötter, 2016; Krüger and Linke, 2011). However, the in vivo substrates and physiological functions of the kinase domains in these proteins are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Twitchin kinase inhibits muscle activity

Matsunaga

Hwang

Franke

et al. 2017

MBoC

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“…Titin is a multifunctional skeletal muscle scaffold protein that spans a half sarcomere from the Z-disc to the M-line, and as a mechanosensor senses alterations of mechanical load (Krüger and Kötter 2016). Through its interaction with various proteins, titin is linked to diverse signaling pathways including hypertrophic signaling (Knöll et al 2011).…”

Section: Titin-based Stretch-sensing Proteins Are Increased After Submentioning

confidence: 99%

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Taatjes

Roth

2017

Histochem Cell Biol

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all resulted in good nuclear immunostaining with the BrdU antibody and acceptable tissue morphology. However, when comparing the effect of the various denaturation agents on cell cycle parameters and phase durations of EGL cells they noted differences in the detection of BrdU-stained cells amongst the reagents, indicating that histological procedures may affect the reproducibility of quantitative analysis of proliferating cells. Taking all of their data into consideration, they recommend that DNase I and citrate buffer may offer less harsh alternatives to hydrochloric acid for DNA denaturation in the BrdU staining protocol. Autophagy and cell survival in cancer, normal, and embryonic cellsAutophagy is a cellular process by which cytoplasmic components are incorporated into autophagocytic vesicles, which eventually fuse with lysosomes resulting in degradation of cellular constituents (Parzych and Klionsky 2014). Over the years, the understanding of this fundamental cellular process has evolved to delineate its critical role in both physiological and pathophysiological mechanisms. Indeed, autophagy has been shown to play the most interesting role in cancer cells, acting as either a tumor suppressor or tumor promoter, with the response related to the type of tumor cell studied. Moreover, similar to apoptosis, autophagy has also been shown to be an important mechanism during vertebrate development (Aburto et al. 2012). Given these diverse roles of autophagy in cellular constituent degradation processes, Rankov et al. (2017) have performed an in-depth analysis to investigate the effect autophagy has on cell survival in model systems (human cancer cells, human normal cells, and zebrafish embryonic cells) treated with anticancer Assessing multiple DNA denaturation pretreatments for BrdU immunostainingThe proliferation state of cells can be assessed via multiple immunostaining protocols, including using antibodies against proliferating cell nuclear antigen (PCNA), Ki-67, and bromodeoxyuridine (BrdU) (Eminaga et al. 2016). Unlike the direct immunostaining for PCNA or Ki-67 on any paraffin-embedded tissue section, BrdU immunostaining requires the prior injection of the thymine analog BrdU into living animals where it incorporates into replicating DNA. The immunostaining procedure then requires section pretreatment with a DNA-denaturing agent to yield single-stranded DNA, a requirement for binding of the anti-BrdU antibody. Typically, denaturation is achieved by section treatment with hydrochloric acid, which may result in a deterioration in both tissue morphological appearance and antigenicity. Since other DNA denaturation agents besides hydrochloric acid have been used in the BrdU immunostaining procedure in previous studies, Molina et al. (2017) have now undertaken a comparative evaluation of the use of a variety of DNA denaturation agents on subsequent BrdU immunostaining, using the transient proliferative rat cerebellar external granular layer (EGL) as a model structure. They found that section pretreatment for partia...

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Titin, a Central Mediator for Hypertrophic Signaling, Exercise-Induced Mechanosignaling and Skeletal Muscle Remodeling

Cited by 95 publications

References 84 publications

Establishment of a highly sensitive sandwich ELISA for the N-terminal fragment of titin in urine

Establishment of a highly sensitive sandwich ELISA for the N-terminal fragment of titin in urine

Twitchin kinase inhibits muscle activity

In focus in HCB

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