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Decrease in membrane phospholipid unsaturation induces unfolded protein response.

Ariyama H, Kono N, Matsuda S, Inoue T, Arai H - J. Biol. Chem. (2010)

Bottom Line: In this study we showed that stearoyl-CoA desaturase 1 (SCD1) knockdown increased the amount of saturated fatty acids and decreased that of monounsaturated fatty acids in phospholipids without affecting the amount or the composition of free fatty acid and induced unfolded protein response (UPR), evidenced by increased expression of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) mRNAs and splicing of Xbox-binding protein 1 (XBP1) mRNA.Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown.These results suggest that a decrease in membrane phospholipid unsaturation induces UPR.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.

ABSTRACT
Various kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues. The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by diet and by altered activities of lipid-metabolizing enzymes such as fatty acid desaturases. However, little is known about how mammalian cells respond to changes in phospholipid fatty acid composition. In this study we showed that stearoyl-CoA desaturase 1 (SCD1) knockdown increased the amount of saturated fatty acids and decreased that of monounsaturated fatty acids in phospholipids without affecting the amount or the composition of free fatty acid and induced unfolded protein response (UPR), evidenced by increased expression of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) mRNAs and splicing of Xbox-binding protein 1 (XBP1) mRNA. SCD1 knockdown-induced UPR was rescued by various unsaturated fatty acids and was enhanced by saturated fatty acid. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), which incorporates preferentially polyunsaturated fatty acids into phosphatidylcholine, was up-regulated in SCD1 knockdown cells. Knockdown of LPCAT3 synergistically enhanced UPR with SCD1 knockdown. Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown. These results suggest that a decrease in membrane phospholipid unsaturation induces UPR.

Show MeSH
LPCAT3 is up-regulated in SCD1 knockdown cells. HeLa cells were transfected with the indicated siRNA. At 66 h after transfection total RNAs were prepared. The expression level of each gene was detected by quantitative real-time PCR. The expression level of each gene was normalized to the GAPDH gene and is represented as -fold induction over siControl. The data represents the mean ± S.E. of three experiments. The asterisks indicate significant differences compared with siControl-transfected cells (p < 0.01).
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Figure 7: LPCAT3 is up-regulated in SCD1 knockdown cells. HeLa cells were transfected with the indicated siRNA. At 66 h after transfection total RNAs were prepared. The expression level of each gene was detected by quantitative real-time PCR. The expression level of each gene was normalized to the GAPDH gene and is represented as -fold induction over siControl. The data represents the mean ± S.E. of three experiments. The asterisks indicate significant differences compared with siControl-transfected cells (p < 0.01).

Mentions: Interestingly, LPCAT3 was significantly up-regulated in SCD1 knockdown cells. Although the expressions of LPCAT1, -2, and -4 were not affected by SCD1 knockdown, LPIAT1 was also slightly up-regulated (Fig. 7).


Decrease in membrane phospholipid unsaturation induces unfolded protein response.

Ariyama H, Kono N, Matsuda S, Inoue T, Arai H - J. Biol. Chem. (2010)

LPCAT3 is up-regulated in SCD1 knockdown cells. HeLa cells were transfected with the indicated siRNA. At 66 h after transfection total RNAs were prepared. The expression level of each gene was detected by quantitative real-time PCR. The expression level of each gene was normalized to the GAPDH gene and is represented as -fold induction over siControl. The data represents the mean ± S.E. of three experiments. The asterisks indicate significant differences compared with siControl-transfected cells (p < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2903364&req=5

Figure 7: LPCAT3 is up-regulated in SCD1 knockdown cells. HeLa cells were transfected with the indicated siRNA. At 66 h after transfection total RNAs were prepared. The expression level of each gene was detected by quantitative real-time PCR. The expression level of each gene was normalized to the GAPDH gene and is represented as -fold induction over siControl. The data represents the mean ± S.E. of three experiments. The asterisks indicate significant differences compared with siControl-transfected cells (p < 0.01).
Mentions: Interestingly, LPCAT3 was significantly up-regulated in SCD1 knockdown cells. Although the expressions of LPCAT1, -2, and -4 were not affected by SCD1 knockdown, LPIAT1 was also slightly up-regulated (Fig. 7).

Bottom Line: In this study we showed that stearoyl-CoA desaturase 1 (SCD1) knockdown increased the amount of saturated fatty acids and decreased that of monounsaturated fatty acids in phospholipids without affecting the amount or the composition of free fatty acid and induced unfolded protein response (UPR), evidenced by increased expression of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) mRNAs and splicing of Xbox-binding protein 1 (XBP1) mRNA.Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown.These results suggest that a decrease in membrane phospholipid unsaturation induces UPR.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.

ABSTRACT
Various kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues. The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by diet and by altered activities of lipid-metabolizing enzymes such as fatty acid desaturases. However, little is known about how mammalian cells respond to changes in phospholipid fatty acid composition. In this study we showed that stearoyl-CoA desaturase 1 (SCD1) knockdown increased the amount of saturated fatty acids and decreased that of monounsaturated fatty acids in phospholipids without affecting the amount or the composition of free fatty acid and induced unfolded protein response (UPR), evidenced by increased expression of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) mRNAs and splicing of Xbox-binding protein 1 (XBP1) mRNA. SCD1 knockdown-induced UPR was rescued by various unsaturated fatty acids and was enhanced by saturated fatty acid. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), which incorporates preferentially polyunsaturated fatty acids into phosphatidylcholine, was up-regulated in SCD1 knockdown cells. Knockdown of LPCAT3 synergistically enhanced UPR with SCD1 knockdown. Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown. These results suggest that a decrease in membrane phospholipid unsaturation induces UPR.

Show MeSH