Faculty Collaboration Database

In vitro and in vivo studies reveal the beneficial effects of chlorogenic acid against ER stress mediated ER-phagy and associated apoptosis in the heart of diabetic rat. Chem Biol Interact 2022 Jan 05;351:109755

Date

11/22/2021

Pubmed ID

34801538

DOI

10.1016/j.cbi.2021.109755

Scopus ID

2-s2.0-85120420272 (requires institutional sign-in at Scopus site)   45 Citations

Abstract

Endoplasmic reticulum (ER) and associated signaling pathways are involved in diabetic cardiomyopathy (DCM) however, detailed studies are not available. The present study investigated the role of ER stress and related pathways such as ER-phagy, apoptosis and their underlying mechanisms using appropriate models. Beneficial effect of chlorogenic acid was also evaluated against ER stress mediated DCM. H9c2 cells with high glucose (33 mM, in vitro model of hyperglycemia) showed significant activation of ER stress response (GRP78, PERK, IRE1α, ATF6α) and altered its regulatory proteins (PDI, ERO1α). Also, it enhanced ER-phagy through upregulation of Sec62, RTN3 and downregulation of FAM134B. High glucose caused apoptosis via increased levels of CHOP, caspase 12 and calnexin. All these proteins (PERK, IRE1α, ATF6α, RTN3, Sec62 and FAM134B) have been found to have a significant role in the functioning of heart such as excitation contraction coupling and we expect these alterations to induce cardiomyopathy during diabetes. This was confirmed in in vivo study too. High fat, high fructose diet with mild streptozotocin induced diabetic rats showed an increased expression of BNP confirming cardiac injury. We also noticed severe ER stress in the heart of diabetic animals. All these have contributed significantly into alterations in histopathology and increase of weight of the hearts. These findings clearly show that ER stress plays a vital protagonist in the progression of DCM. We also found chlorogenic acid is effective against hyperglycemia induced pathological alteration both in vitro as well as in vivo.

Author List

Preetha Rani MR, Salin Raj P, Nair A, Ranjith S, Rajankutty K, Raghu KG

Author

Anupama Nair Postdoctoral Researcher 3 in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Autophagy
Cell Line
Chlorogenic Acid
Diabetes Mellitus, Experimental
Diabetic Cardiomyopathies
Endoplasmic Reticulum
Endoplasmic Reticulum Stress
Heart
Hyperglycemia
Male
Myocardium
Rats
Rats, Wistar
Signal Transduction