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Possible Molecular Chaperones for Lipoprotein Lipase in Endoplasmic Reticulum
Yang, Jeong-Yeh,Kim, Mee-Ae,Koo, Bon-Sun,Kim, Sun-Mee,Park, Jin-Woo Korean Society for Biochemistry and Molecular Biol 1999 Journal of biochemistry and molecular biology Vol.32 No.3
Studies in adipocytes indicate that secretion of active lipoprotein lipase (LPL) was strictly regulated by a quality control system in the endoplasmic reticulum (ER). However, there has been no report about the ER chaperones participating in the folding and assembly of LPL. Many chaperones are known to bind unfolded proteins and dissociate from them through the ATP-hydrolyzing reaction. In this study, putative ER chaperones for LPL were determined by affinity chromatography using denatured LPL as an affinity ligand and elution with ATP. BiP, grp94, calreticulin, and another 50 kDa K-D-E-L protein in the ER of rat adipose tissue were bound to denatured LPL and eluted by ATP. Calnexin was bound to denatured LPL; however, it was not eluted by ATP but by acetic acid. These results indicate that, at least, BiP, grp94, calreticulin, calnexin, and the unidentified 50 kDa protein might act as putative chaperones for the proper folding and assembly of LPL in ER.
Octanoate and Decanoate Induce Apoptosis in 3T3-L1 Adipocytes
Jeong-Yeh Yang,Srujana Rayalam,Mary Anne Della-Fera,Suresh Ambati,Clifton A. Baile 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.5
The effect of octanoate and decanoate, respectively, eight- and 10-carbon medium-chain fatty acids (MCFAs), on apoptotic signaling in 3T3-L1 adipocytes was investigated. 3T3-L1 adipocytes were treated with various concentrations of octanoate or decanoate. Cell viability, apoptosis, and expression of apoptosis-related proteins were investigated. Results indicated that both octanoate and decanoate decreased viability, increased apoptosis, and increased reactive oxygen species production. Immunoblotting analysis showed an increase in the levels of cytoplasmic cytochrome c and cleaved poly(ADP-ribose) polymerase by octanoate and decanoate. Concomitantly, we observed that pro-caspase-3 was decreased, resulting in the induced accumulation of the cleaved form of caspase-3 by both octanoate and decanoate. In addition, both octanoate and decanoate increased the expression of pro-apoptotic Bax with an accompanied decrease of anti-apoptotic Bcl-2. These results show that octanoate and decanoate mediate adipocyte apoptosis via a caspase-dependent mitochondrial pathway in 3T3-L1 adipocytes. MCFAs thus decrease adipocyte number by initiating the apoptotic process in 3T3-L1 adipocytes.
Anti-Obesity Effects of Xanthohumol Plus Guggulsterone in 3T3-L1 Adipocytes
Rayalam, Srujana,Yang, Jeong-Yeh,Della-Fera, Mary Anne,Park, Hea-Jin,Ambati, Suresh,Baile, Clifton A. The Korean Society of Food Science and Nutrition 2009 Journal of medicinal food Vol.12 No.4
Xanthohumol (XN) and guggulsterone (GS) have each been shown to inhibit adipogenesis and induce apoptosis in adipocytes. In the present study effects of the combination of XN+GS on 3T3-L1 adipocyte apoptosis and adipogenesis were investigated. Mature adipocytes were treated with XN and GS individually and in combination. XN and GS individually decreased cell viability, but XN+GS caused an enhanced decrease in viability and potentiated induction of apoptosis. Likewise, XN+GS caused a potentiated increase in caspase-3/7 activation, whereas neither of the compounds showed any effect individually. In addition, western blot analysis revealed that XN+GS increased Bax expression and decreased Bcl-2 expression, whereas individual compounds did not show any significant effect. XN and GS both decreased lipid accumulation. Individually, XN at $1.5\;{\mu}M$ and GS at $3.12\;{\mu}M$ decreased lipid accumulation by $26\;{\pm}\;4.5%$ (P < .001) each, whereas XN1.5+GS3.12 decreased lipid accumulation by $78.2\;{\pm}\;1.8% (P < .001). Moreover, expression of the adipocyte-specific proteins was down-regulated with XN1.5+GS3.12, but no effect was observed with the individual compounds. Finally, XN+GS caused an enhanced stimulation of lipolysis. Thus, combination of XN and GS is more potent in exerting anti-obesity effects than additive effects of the individual compounds.
Anti-Obesity Effects of Xanthohumol Plus Guggulsterone in 3T3-L1 Adipocytes
Srujana Rayalam,Jeong-Yeh Yang,Mary Anne Della-Fera,Hea Jin Park,Suresh Ambati,Clifton A. Baile 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.4
Xanthohumol (XN) and guggulsterone (GS) have each been shown to inhibit adipogenesis and induce apoptosis in adipocytes. In the present study effects of the combination of XN+GS on 3T3-L1 adipocyte apoptosis and adipogenesis were investigated. Mature adipocytes were treated with XN and GS individually and in combination. XN and GS individually decreased cell viability, but XN+GS caused an enhanced decrease in viability and potentiated induction of apoptosis. Likewise, XN+GS caused a potentiated increase in caspase-3/7 activation, whereas neither of the compounds showed any effect individually. In addition, western blot analysis revealed that XN+GS increased Bax expression and decreased Bcl-2 expression, whereas individual compounds did not show any significant effect. XN and GS both decreased lipid accumulation. Individually, XN at 1.5μM and GS at 3.12μM decreased lipid accumulation by 26±4.5% (P<.001) each, whereas XN1.5+GS3.12 decreased lipid accumulation by 78.2±1.8% (P<.001). Moreover, expression of the adipocyte-specific proteins was down-regulated with XN1.5+GS3.12, but no effect was observed with the individual compounds. Finally, XN+GS caused an enhanced stimulation of lipolysis. Thus, combination of XN and GS is more potent in exerting anti-obesity effects than additive effects of the individual compounds.
Possible Molecular Chaperones for Lipoprotein Lipase in Endoplasmic Reticulum
Park, Jin Woo,Yang, Jeong Yeh,Kim, Mee Ae,Koo, Bon Sun,Kim, Sun Mee 생화학분자생물학회 2000 BMB Reports Vol.32 No.3
Studies in adipocytes indicate that secretion of active lipoprotein lipase (LPL) was strictly regulated by a quality control system in the endoplasmic reticulum (ER). However, there has been no report about the ER chaperones participating in the folding and assembly of LPL. Many chaperones are known to bind unfolded proteins and dissociate from them through the ATP-hydrolyzing reaction. In this study, putative ER chaperones for LPL were determined by affinity chromatography using denatured LPL as an affinity ligand and elution with ATP BiP, grp94, calreticulin, and another 50 kDa K-D-E-L protein in the ER of rat adipose tissue were bound to denatured LPL and eluted by ATP. Calnexin was bound to denatured LPL; however, it was not eluted by ATP but by acetic acid. These results indicate that, at least, BiP, grp94, calreticulin, calnexin, and the unidentified 50 kDa protein might act as putative chaperones for the proper folding and assembly of LPL in ER.
Preventing Bone Loss and Weight Gain with Combinations of Vitamin D and Phytochemicals
Ching-Yi Lai,Jeong-Yeh Yang,Srujana Rayalam,Mary Anne Della-Fera,Suresh Ambati,Richard D. Lewis,Mark W. Hamrick,Diane L. Hartzell,Clifton A. Baile 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.11
Vitamin D and certain natural compounds have been shown to regulate both lipid metabolism and bone formation. Treatments that prevent or reverse age-related increase in bone marrow adiposity could both increase new bone formation and inhibit bone destruction. We tested the hypothesis that dietary supplementation with combinations of vitamin D and phytochemicals inhibits bone loss and decreases adiposity to a greater extent than control or vitamin D–alone diets. Aged ovariectomized female rats (12 months old, n=50, initial body weight=240 g) were given control (AIN-93M diet), vitamin D (2,400 IU/kg), or vitamin D plus resveratrol (16, 80, or 400 mg/kg of diet [low, medium, and high dose, respectively]), quercetin (80, 400, or 2,000 mg/kg of diet), and genistein (64, 256, or 1,040 mg/kg of diet) for 8 weeks. The high-dose treatment (vitamin D+400 mg/kg resveratrol+2,000 mg/kg quercetin+1,040 mg/kg genistein) reduced body weight gain (P<.05) and the fat pad weights (P<.05). This treatment also increased the serum concentration of insulin-like growth factor-1 (P<.05) and the bone mineral content of the femur. Micro-computed tomography and histomorphometric analyses indicated that the high-dose treatment prevented loss of trabecular bone (P<.05) and reduced marrow adipocytes (P<.001) and osteoclasts (P<.05) compared with the control and vitamin D alone (P<.05). We conclude that aged ovariectomized female rats supplemented with vitamin D combined with genistein, quercetin, and resveratrol had improved bone mineral density and reduced body weight gain and a significant decrease in bone marrow adipocytes. The synergistic effects of a combination of phytochemicals with vitamin D may be effective in reducing bone loss and weight gain after menopause.