Autophagy is altered in skeletal and cardiac muscle of spontaneously hypertensive rats. (5th November 2013)

• Record Type: Journal Article
• Authors: Bloemberg, D.; McDonald, E.; Dulay, D.; Quadrilatero, J.
• Is Part Of: Acta physiologica. Volume 210:Number 2(2014:Feb.)
• Page Start: 381
• Page End: 391
• Publication Date: 2013-11-05
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12178
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" id="apha12178-abs-0001"> <title>Abstract</title> <sec id="apha12178-sec-0001" sec-type="section"> <title>Aim</title> <p>Autophagy is a subcellular degradation mechanism important for muscle maintenance. Hypertension induces well‐characterized pathological changes to the heart and is associated with impaired function and increased apoptotic signalling in skeletal muscle. We examined whether essential hypertension affects several autophagy markers in skeletal and cardiac muscle.</p> </sec> <sec id="apha12178-sec-0002" sec-type="section"> <title>Methods</title> <p>Immunoblotting and qRT‐PCR were used to measure autophagy‐related proteins/mRNA in multiple skeletal muscles as well as left ventricle (LV) of spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY).</p> </sec> <sec id="apha12178-sec-0003" sec-type="section"> <title>Results</title> <p>Skeletal muscles of hypertensive rats had decreased (<italic>P</italic> < 0.01) cross‐sectional area of type I fibres (e.g. soleus WKY: 2952.9 ± 64.4 μm<sup>2</sup> vs. SHR: 2579.9 ± 85.8 μm<sup>2</sup>) and a fibre redistribution towards a 'fast' phenotype. Immunoblot analysis revealed that some SHR skeletal muscles displayed a decreased LC3II/I ratio (<italic>P</italic> < 0.05), but none showed differences in p62 protein. LC3 and LAMP2 mRNA levels were increased approx. 2–3‐fold in all skeletal muscles (<italic>P</italic> < 0.05), while cathepsin activity, cathepsin L mRNA and Atg7 protein were increased 16–17% (<italic>P</italic> < 0.01), 2–3‐fold (<italic>P</italic> < 0.05) and 29–49% (<italic>P</italic> < 0.01), respectively, in fast muscles of hypertensive animals. Finally, protein levels of BAG3, a marker of chaperone‐assisted selective autophagy, were 18–25% lower (<italic>P</italic> < 0.05) in SHR skeletal muscles. In the LV of SHR, LC3I and p62 protein were elevated 34% (<italic>P</italic> < 0.05) and 47% (<italic>P</italic> < 0.01), respectively. Furthermore, p62 mRNA was 68% higher (<italic>P</italic> < 0.05), while LAMP2 mRNA was 45% lower (<italic>P</italic> < 0.05), in SHR cardiac muscle. There was no difference in Beclin1, Atg7, Bnip3 or BAG3 protein in the LV between strains.</p> </sec> <sec id="apha12178-sec-0004" sec-type="section"> <title>Conclusion</title> <p>These results suggest that autophagy is altered in skeletal and cardiac muscle during hypertension.</p> </sec> </abstract>