title: Endoplasmic reticulum stress in diabetic mouse or glycated LDL-treated endothelial cells: protective effect of Saskatoon berry powder and cyanidin glycans.
abstract: Endoplasmic reticulum (ER) stress is associated with insulin resistance and diabetic cardiovascular complications, and mechanism or remedy for ER stress remains to be determined. The results of the present study demonstrated that the levels of ER stress or unfolded protein response (UPR) markers, the intensity of thioflavin T (ThT) fluorescence and the abundances of GRP78/94, XBP-1 and CHOP proteins were elevated in cardiovascular tissue of diabetic leptin receptor-deficient (db/db) mice. Cyanidin-3-glucoside (C3G) and cyanidin-3-galactoside (C3Ga) are major anthocyanins in Saskatoon berry (SB) powder. The administration of 5% SB powder for 4 weeks attenuated ThT fluorescence and the UPR markers in hearts and aortae of wild-type and db/db mice. Treatment with glycated low-density lipoprotein (gLDL) increased ThT intensity in human umbilical vein endothelial cells (ECs). Elevated UPR markers were detected in gLDL-treated EC compared to control cultures. The involvement of ER stress in gLDL-treated EC was supported by that the addition of 4-phenyl butyrate acid (a known ER stress antagonist) inhibited gLDL-induced increases in ER stress or UPR markers. C3G at 30 μM or C3Ga at 100 μM reached their maximal inhibition on gLDL-induced increases in ThT, GRP78/94, XBP-1 and CHOP in EC. The results demonstrated that ER stress was enhanced in cardiovascular tissue of db/db mice or gLDL-treated EC. SB powder or cyanidin glycans prevented the abnormal increases in ER stress and UPR markers in cardiovascular tissue of diabetic db/db mice or gLDL-treated EC.
authors.affiliation: Department of Internal Medicine, Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Ruozhi
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Internal Medicine, Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Xueping
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Khuong
authors.initials: K
authors.lastname: Le
authors.affiliation: Department of Food Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Wende
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Moghadasian
authors.affiliation: Department of Food Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Trust
authors.initials: T
authors.lastname: Beta
authors.affiliation: Department of Internal Medicine, Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address: garry.shen@med.umanitoba.ca.
authors.forename: Garry X
authors.initials: GX
authors.lastname: Shen
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D052160:Benzothiazoles; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005697:Galactosides / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D011208:Powders / Q000737:chemistry; D020011:Protective Agents / Q000494:pharmacology; D027824:Rosaceae / Q000737:chemistry*; D013844:Thiazoles; D051742:Transcription Factor CHOP / Q000378:metabolism; D056811:Unfolded Protein Response / Q000187:drug effects; D000071717:X-Box Binding Protein 1 / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D052160:Benzothiazoles; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D005697:Galactosides; D005960:Glucosides; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D008077:Lipoproteins, LDL; D011208:Powders; D020011:Protective Agents; D013844:Thiazoles; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; C462279:cyanidin-3-O-beta-glucopyranoside; D051742:Transcription Factor CHOP; C009462:thioflavin T; C546035:cyanidin 3-galactoside
keywords: Cyanidin glycans; Endoplasmic reticulum stress; Endothelial cells; Glycated LDL; Saskatoon berry; db/db mice