Lipoprotein lipase is expressed in cultured Schwann cells and functions in lipid synthesis and utilization

Abstract

We have previously demonstrated that lipoprotein lipase (LPL; triacylglycero-protein acylhydrolase, EC 3.1.1.34) is most likely expressed in the non-neuronal cells of the spinal cord, and glial cells may thus be the site of expression in the peripheral nervous system as well. We investigated the expression of LPL in cultured 1.17 cells, an immortalized rat sciatic nerve Schwann cell line. The 1.17 cells were shown to express LPL mRNA by reverse transcriptase-polymerase chain reaction analysis. The 1.17 Schwann cells demonstrated heparin-releasable lipolytic activity that was inhibited by the lipase inhibitor tetrahydrolipstatin in a dosedependent manner. Preincubation of 1.17 cells with an antirat LPL antiserum reduced the heparin-releasable lipolytic activity to Ͻ 10% of that measured in untreated cells. To investigate the role of LPL in Schwann cell lipid metabolism, 1.17 cells were incubated for up to 24 h with an emulsified [ 14 C]triolein substrate and the incorporation of [ 14 C]triolein radioactivity into various cellular lipids was examined in the presence of either anti-rat LPL antiserum or preimmune serum. Inhibiting LPL activity reduced the incorporation of 14 C into cellular polar lipids, diacylglycerol, and cholesteryl esters by Ͼ 80% at 2 and 6 h after addition of the radiolabeled substrate. At 24 h, radioactivity in diacylglycerol and cholesteryl esters was similar in cells treated with anti-LPL antiserum or preimmune serum, whereas 14 C incorporation into polar lipids was still reduced by Ͼ 60%. Separation of the polar lipids into individual lipid species revealed no specific changes in triolein-derived radioactivity incorporation across the phospholipid species examined. These results suggest that LPL-mediated hydrolysis of exogenous triacylglycerol is an important source of free fatty acids for the Schwann cell and thus may play a critical role in myelin biosynthesis in the peripheral nervous system.

Lipoprotein Lipase (LPL) is Associated with Neurite Pathology and Its Levels Are Markedly Reduced in the Dentate Gyrus of Alzheimer’s Disease Brains

“…In our study, LPL immunoreactivity was widely present throughout all major regions of human brain tissue, with moderate to high immunoreactivity in subgroups of neurons, extensive immunoreactivity in microglia, and sporadic immunoreactivity in astrocytes and oligodendroglia. LPL immunostaining in Schwann cells associated with cranial nerves is in agreement with previously published in vitro data (Huey et al 1998 andFerreira et al 2002), and the presence of LPL in the brain microvasculature supports findings in the rat brain (Shirai et al 1986).…”

Lipoprotein lipase is expressed in rat sciatic nerve and regulated in response to crush injury

“…We have previously shown that LPL mRNA and cell-surface activity are expressed by cultured Schwann cells isolated from rat peripheral nerve. Inhibiting LPL activity with a polyclonal anti-LPL antiserum inhibited the cells' ability to utilize exogenous triacylglycerol-derived FFA for incorporation into newly synthesized phospholipids, triacylglycerol, and cholesteryl esters (6). Based on these results, we hypothesized that LPL in the nerve functions in maintenance of nerve myelin and may be involved in the recycling of myelin lipids that occurs upon nerve injury.…”

“…Approximately equalsized portions of the contralateral uninjured ner ves were treated likewise. Duplicate aliquots of the supernatants were assayed for LPL activity as described (6), and data are expressed as nEq of FFA released per min per g nerve tissue.…”

“…Total RNA was isolated according to the manufacturer's instructions. 1 g of total RNA was subjected to reverse transcription-polymerase chain reaction (RT-PCR) quantification of LPL utilizing primers specific for LPL and 18S ribosomal RNA as described (6). Data are expressed as the relative ratio of LPL mRNA:18S rRNA in each segment.…”

“…We have previously demonstrated that LPL is expressed by immortalized Schwann cells in vitro and functions to allow utilization of exogenous triacylglycerol for de novo lipid biosynthesis (6). We hypothesized that expression of LPL in the peripheral nerve may function to help maintain myelin lipid and to allow lipid reutilization from the myelin lipids degraded during injury-induced nerve degeneration.…”