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Relation of nNOS isoforms to mitochondrial density and PGC-1alpha expression in striated muscles of mice. | LitMetric

AI Article Synopsis

  • This study investigates the expression of neuronal NO synthase (nNOS) isoforms in skeletal muscle and their relationship with mitochondrial content and activity, particularly focusing on the role of the PGC-1alpha coactivator.
  • Research using various mouse models found that nNOS alpha-isoform predominates in type-2 oxidative muscle fibers and is linked to higher mitochondrial density, especially in the tibialis anterior muscle compared to other muscles.
  • The findings suggest that nNOS alpha-isoform expression is positively regulated by PGC-1alpha, indicating a significant interaction between nNOS and mitochondrial signaling in oxidative muscle fibers.

Article Abstract

The expression of neuronal NO synthase (nNOS) alpha- and beta-isoforms in skeletal muscle is well documented but only little information is available about their regulation/functions. Using different mouse models, we now assessed whether the expression of nNOS-isoforms in muscle fibers is related to mitochondria content/activity and regulated by peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). Catalytic histochemistry revealed highest nNOS-concentrations to be present in type-2 oxidative muscle fibers. Differences in mitochondrial density between nNOS-KO-mice and WT-littermates established by morphometry after transmission electron microscopy were significant in the oxidative portion of the tibialis anterior muscle (TA) but not in rectus femoris muscle (RF) indicating an nNOS-dependent mitochondrial pool in TA. Quantitative immunoblotting displayed the nNOS alpha-isoform to preponderate in those striated muscles of C57BL/6-mice that comprise of many type-2 oxidative fibers, e.g. TA, while roughly even levels of the two nNOS-isoforms were expressed in those muscles that mainly consist of type-2 glycolytic fibers, e.g. RF. Differences in citrate synthase-activity in muscle homogenates between nNOS-KO-mice and WT-littermates were positively related to nNOS alpha-isoform levels. In transgenic-mice over-expressing muscular PGC-1alpha compared to WT-littermates, immunoblotting revealed a significant shift in nNOS-expression in favor of the alpha-isoform in six out of eight striated muscles (exceptions: soleus muscle and tongue) without consistent relationship to changes in the expression of mitochondrial markers. In summary, our study demonstrated the nNOS alpha-isoform expression to be related to mitochondrial content/activity and to be up-regulated by up-stream PGC-1alpha in striated muscles, particularly in those enriched with type-2 oxidative fibers implying a functional convergence of the two signaling systems in these fibers.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697538PMC
http://dx.doi.org/10.1016/j.niox.2018.04.005DOI Listing

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