Ankrd2 in Mechanotransduction and Oxidative Stress Response in Skeletal Muscle: New Cues for the Pathogenesis of Muscular Laminopathies

Ankrd2 (ankyrin repeats containing domain 2) or Arpp (ankyrin repeat, PEST sequence, and proline-rich region) is a member of the muscle ankyrin repeat protein family. Ankrd2 is mostly expressed in skeletal muscle, where it plays an intriguing role in the transcriptional response to stress induced by mechanical stimulation as well as by cellular reactive oxygen species. Our studies in myoblasts from Emery-Dreifuss muscular dystrophy 2, a LMNA-linked disease affecting skeletal and cardiac muscles, demonstrated that Ankrd2 is a lamin A-binding protein and that mutated lamins found in Emery-Dreifuss muscular dystrophy change the dynamics of Ankrd2 nuclear import, thus affecting oxidative stress response. In this review, besides describing the latest advances related to Ankrd2 studies, including novel discoveries on Ankrd2 isoform-specific functions, we report the main findings on the relationship of Ankrd2 with A-type lamins and discuss known and potential mechanisms involving defective Ankrd2-lamin A interplay in the pathogenesis of muscular laminopathies.

Download Full-text

Autoinducer-2 Triggers the Oxidative Stress Response in Mycobacterium avium, Leading to Biofilm Formation

Applied and Environmental Microbiology ◽

10.1128/aem.02066-07 ◽

2008 ◽

Vol 74 (6) ◽

pp. 1798-1804 ◽

Cited By ~ 51

Author(s):

Henriette Geier ◽

Serge Mostowy ◽

Gerard A. Cangelosi ◽

Marcel A. Behr ◽

Timothy E. Ford

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Quorum Sensing ◽

Mycobacterium Avium ◽

Biofilm Formation ◽

Transcriptional Response ◽

Opportunistic Pathogen ◽

Environmental Stresses ◽

Oxidative Stress Response ◽

Autoinducer 2

ABSTRACT Mycobacterium avium is an environmental organism and opportunistic pathogen with inherent resistance to drugs, environmental stresses, and the host immune response. To adapt to these disparate conditions, M. avium must control its transcriptional response to environmental cues. M. avium forms biofilms in various environmental settings, including drinking water pipes and potable water reservoirs. In this study, we investigated the role of the universal signaling molecule autoinducer-2 (AI-2) in biofilm formation by M. avium. The addition of the compound to planktonic M. avium cultures resulted in increased biofilm formation. Microarray and reverse transcriptase PCR studies revealed an upregulation of the oxidative stress response upon addition of AI-2. This suggests that the response to AI-2 might be related to oxidative stress, rather than quorum sensing. Consistent with this model, addition of hydrogen peroxide, a known stimulus of the oxidative stress response, to M. avium cultures resulted in elevated biofilm formation. These results suggest that AI-2 does not act as a quorum-sensing signal in M. avium. Instead, biofilm formation is triggered by environmental stresses of biotic and abiotic origins and AI-2 may exert effects on that level.

Download Full-text

Eccentric Exercise Affects NRF2-mediated Oxidative Stress Response in Skeletal Muscle by Increasing Nuclear NRF2 Content

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000401057.84779.de ◽

2011 ◽

Vol 43 (Suppl 1) ◽

pp. 383 ◽

Cited By ~ 2

Author(s):

Lauren G. MacNeil ◽

Adeel Safdar ◽

Steven K. Baker ◽

Simon Melov ◽

Mark A. Tarnopolsky

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Stress Response ◽

Eccentric Exercise ◽

Oxidative Stress Response

Download Full-text

Altered modulation of lamin A/C-HDAC2 interaction and p21 expression during oxidative stress response in HGPS

Aging Cell ◽

10.1111/acel.12824 ◽

2018 ◽

Vol 17 (5) ◽

pp. e12824 ◽

Cited By ~ 17

Author(s):

Elisabetta Mattioli ◽

Davide Andrenacci ◽

Cecilia Garofalo ◽

Sabino Prencipe ◽

Katia Scotlandi ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Oxidative Stress Response ◽

Lamin A

Download Full-text

Denervation does not induce muscle atrophy through oxidative stress

European Journal of Translational Myology ◽

10.4081/ejtm.2017.6406 ◽

2017 ◽

Vol 27 (1) ◽

Cited By ~ 8

Author(s):

Eva Pigna ◽

Emanuela Greco ◽

Giulio Morozzi ◽

Silvia Grottelli ◽

Alessio Rotini ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Stress Response ◽

Muscle Atrophy ◽

Oxidative Stress Response ◽

Skeletal Muscle Atrophy ◽

Molecular Pathways ◽

Ubiquitin Proteasome ◽

Anti Oxidant ◽

Kinetics Of

Denervation leads to the activation of the catabolic pathways, such as the ubiquitin-proteasome and autophagy, resulting in skeletal muscle atrophy and weakness. Furthermore, denervation induces oxidative stress in skeletal muscle, which is thought to contribute to the induction of skeletal muscle atrophy. Several muscle diseases are characterized by denervation, but the molecular pathways contributing to muscle atrophy have been only partially described. Our study delineates the kinetics of activation of oxidative stress response in skeletal muscle following denervation. Despite the denervation-dependent induction of oxidative stress in skeletal muscle, treatments with anti-oxidant drugs do not prevent the reduction of muscle mass. Our results indicate that, although oxidative stress may contribute to the activation of the response to denervation, it is not responsible by itself of oxidative damage or neurogenic muscle atrophy.

Download Full-text

Transcriptional Response of Leptospira interrogans to Iron Limitation and Characterization of a PerR Homolog

Infection and Immunity ◽

10.1128/iai.00435-10 ◽

2010 ◽

Vol 78 (11) ◽

pp. 4850-4859 ◽

Cited By ~ 54

Author(s):

Miranda Lo ◽

Gerald L. Murray ◽

Chen Ai Khoo ◽

David A. Haake ◽

Richard L. Zuerner ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Iron Homeostasis ◽

Storage Proteins ◽

Iron Acquisition ◽

Bacterial Species ◽

Transcriptional Response ◽

Oxidative Stress Response ◽

Wild Type ◽

In The Wild

ABSTRACT Leptospirosis is a globally significant zoonosis caused by Leptospira spp. Iron is essential for growth of most bacterial species. Since iron availability is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur. L. interrogans encodes four predicted Fur homologs; we have constructed a mutation in one of these, la1857. We conducted microarray analysis to identify iron-responsive genes and to study the effects of la1857 mutation on gene expression. Under iron-limiting conditions, 43 genes were upregulated and 49 genes were downregulated in the wild type. Genes encoding proteins with predicted involvement in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were overrepresented in the upregulated list, while 54% of differentially expressed genes had no known function. There were 16 upregulated genes of unknown function which are absent from the saprophyte L. biflexa and which therefore may encode virulence-associated factors. Expression of iron-responsive genes was not significantly affected by mutagenesis of la1857, indicating that LA1857 is not a global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and a putative catalase in the mutant suggested that LA1857 is more similar to PerR, a regulator of the oxidative stress response. Indeed, the la1857 mutant was more resistant to peroxide stress than the wild type. Our results provide insights into the role of iron in leptospiral metabolism and regulation of the oxidative stress response, including genes likely to be important for virulence.

Download Full-text