Diminished muscle growth in the obese Zucker rat following overload is associated with hyperphosphorylation of AMPK and dsRNA-dependent protein kinase

作者：Katta Anjaiah; Kakarla Sunil K; Manne Nandini D P K; Wu Miaozong; Kundla Sudarsanam; Kolli Madhukar B; Nalabotu Siva K; Blough Eric R^*

来源：Journal of Applied Physiology, 2012, 113(3): 377-384.

DOI：10.1152/japplphysiol.00397.2011

• obese Zucker rat
• skeletal muscle
• hypertrophy

Katta A, Kakarla SK, Manne ND, Wu M, Kundla S, Kolli MB, Nalabotu SK, Blough ER. Diminished muscle growth in the obese Zucker rat following overload is associated with hyperphosphorylation of AMPK and dsRNA-dependent protein kinase. J Appl Physiol 113: 377-384, 2012. First published May 31, 2012; doi:10.1152/japplphysiol.00397.2011.-Previous data have suggested that insulin-resistant skeletal muscle may exhibit a diminished ability to undergo hypertrophy and that this result may be mediated, at least in part, from decrements in mammalian target of rapamycin (mTOR) signaling (Katta A, Kundla S, Kakarla SK, Wu M, Fannin J, Paturi S, Liu H, Addagarla HS, Blough ER. Am J Physiol Regul Integr Comp Physiol 299: R1666-R1675, 2010). Herein, we attempt to extend these observations by determining if this attenuation in muscle growth is associated with alterations in AMP-activated protein kinase (AMPK) signaling, an upstream mediator of mTOR, and changes in the activation of dsRNA-dependent protein kinase (PKR), which functions as an inhibitor of protein synthesis and potential mediator of protein degradation. Compared with that observed in lean Zucker (LZ) rats, the phosphorylation of AMPK alpha at Thr172 was higher after 3 wk of overload in the insulin-resistant obese Zucker (OZ) soleus (P < 0.05). This change in AMPK alpha phosphorylation was accompanied by increases in the amount of phosphorylated PKR (Thr446), elevations in the PKR-dependent phosphorylation of eukaryotic initiation factor (eIF)-2 alpha (Ser51), augmented p38 MAP kinase (Thr180/Tyr182) phosphorylation, and increases in the amount of protein ubiquitination (P < 0.05). Taken together, these results suggest that the diminished hypertrophic response we observe in the OZ rat may be mediated, at least in part, by the hyperactivation of AMPK- and PKR-related signaling.

• 出版日期2012-8