engleski

Neuropathy target esterase-related enzyme: a possible role in skeletal muscle energy metabolism

Neuropathy target esterase-related enzyme (NRE, PNPLA7), a serine esterase and a member of the family of patatin-like phospholipase domain containing enzymes, is a trans-membrane protein linked to the endoplasmic reticulum and to the lipid droplets in adipocytes and some other cell types and tissues. While NRE has been identified as a lysophospholipase that hydrolyzes sn-1 esters in lysophosphatidylcholine and lysophosphatidic acid, its physiological roles have not been thoroughly examined. The objective of our study was to investigate NRE expression and its functional characteristics in skeletal muscle. Here we found that cultured human skeletal muscle cells express NRE mRNA and protein. Furthermore, by using p-nitrophenyl valerate assay we detected specific NRE activity in these cells. Taken together, our data show that human skeletal muscle cells possess functional NRE. Since skeletal muscles represent approximately 40% of body weight and are one of the key metabolic tissues, we have evaluated a possible role of NRE in skeletal muscle energy metabolism. To investigate whether NRE expression is regulated by substrate availability or by metabolic hormones, we exposed human skeletal muscle cells to different concentrations of glucose, insulin or forskolin, a cell-permeable activator of adenylyl cyclase that mimics effects of insulin antagonists like adrenaline. Insulin treatment tended to suppress NRE expression. Conversely, NRE expression was increased by forskolin, suggesting a role for adrenaline in regulation of NRE expression. Effects of insulin were, in part, dependent upon glucose concentration. Insulin-induced suppression of NRE expression was especially pronounced when skeletal muscle cells were exposed to high (4, 5 g/L) glucose concentration. In contrast, normal (1 g/L) glucose concentration blunted suppressive effects of insulin on NRE expression. These results suggest that NRE expression in human skeletal muscle might fluctuate during the starve-feed cycle. Collectively, our results demonstrate that human skeletal muscle cells possess a functional NRE. They indicate that metabolic hormones and glucose concentration regulate expression of NRE in human skeletal muscle cells, therefore implicating a role for NRE in skeletal muscle energy metabolism. Acknowledgment: This work was supported by the Croatian-Slovenian bilateral grant (2014-2015 PIs: M. Katalinić and T. Marš) and grant P3-0043 from the Slovenian Research Agency.

NRE; patatin like phospholipase

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