Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes

Luong Dai Ly, Shanhua Xu, Seong Kyung Choi, Chae Myeong Ha, Themis Thoudam, Seung Kuy Cha, Andreas Wiederkehr, Claes B. Wollheim, In Kyu Lee, Kyu Sang Park

Research output: Contribution to journalReview article

53 Citations (Scopus)

Abstract

Free fatty acids (FFAs) are important substrates for mitochondrial oxidative metabolism and ATP synthesis but also cause serious stress to various tissues, contributing to the development of metabolic diseases. CD36 is a major mediator of cellular FFA uptake. Inside the cell, saturated FFAs are able to induce the production of cytosolic and mitochondrial reactive oxygen species (ROS), which can be prevented by co-exposure to unsaturated FFAs. There are close connections between oxidative stress and organellar Ca 2+ homeostasis. Highly oxidative conditions induced by palmitate trigger aberrant endoplasmic reticulum (ER) Ca 2+ release and thereby deplete ER Ca 2+ stores. The resulting ER Ca 2+ deficiency impairs chaperones of the protein folding machinery, leading to the accumulation of misfolded proteins. This ER stress may further aggravate oxidative stress by augmenting ER ROS production. Secondary to ER Ca 2+ release, cytosolic and mitochondrial matrix Ca 2+ concentrations can also be altered. In addition, plasmalemmal ion channels operated by ER Ca 2+ depletion mediate persistent Ca 2+ influx, further impairing cytosolic and mitochondrial Ca 2+ homeostasis. Mitochondrial Ca 2+ overload causes superoxide production and functional impairment, culminating in apoptosis. This vicious cycle of lipotoxicity occurs in multiple tissues, resulting in β-cell failure and insulin resistance in target tissues, and further aggravates diabetic complications.

Original languageEnglish
Article numbere291
JournalExperimental and Molecular Medicine
Volume49
Issue number2
DOIs
Publication statusPublished - 2017 Feb 3

Fingerprint

Oxidative stress
Palmitic Acid
Medical problems
Nonesterified Fatty Acids
Endoplasmic Reticulum
Type 2 Diabetes Mellitus
Oxidative Stress
Tissue
Reactive Oxygen Species
Protein folding
Palmitates
Homeostasis
Ion Channels
Metabolism
Superoxides
Machinery
Endoplasmic Reticulum Stress
Adenosine Triphosphate
Protein Folding
Metabolic Diseases

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Ly, Luong Dai ; Xu, Shanhua ; Choi, Seong Kyung ; Ha, Chae Myeong ; Thoudam, Themis ; Cha, Seung Kuy ; Wiederkehr, Andreas ; Wollheim, Claes B. ; Lee, In Kyu ; Park, Kyu Sang. / Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes. In: Experimental and Molecular Medicine. 2017 ; Vol. 49, No. 2.
@article{749f6ba01ad54c279cae2441e320fbbb,
title = "Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes",
abstract = "Free fatty acids (FFAs) are important substrates for mitochondrial oxidative metabolism and ATP synthesis but also cause serious stress to various tissues, contributing to the development of metabolic diseases. CD36 is a major mediator of cellular FFA uptake. Inside the cell, saturated FFAs are able to induce the production of cytosolic and mitochondrial reactive oxygen species (ROS), which can be prevented by co-exposure to unsaturated FFAs. There are close connections between oxidative stress and organellar Ca 2+ homeostasis. Highly oxidative conditions induced by palmitate trigger aberrant endoplasmic reticulum (ER) Ca 2+ release and thereby deplete ER Ca 2+ stores. The resulting ER Ca 2+ deficiency impairs chaperones of the protein folding machinery, leading to the accumulation of misfolded proteins. This ER stress may further aggravate oxidative stress by augmenting ER ROS production. Secondary to ER Ca 2+ release, cytosolic and mitochondrial matrix Ca 2+ concentrations can also be altered. In addition, plasmalemmal ion channels operated by ER Ca 2+ depletion mediate persistent Ca 2+ influx, further impairing cytosolic and mitochondrial Ca 2+ homeostasis. Mitochondrial Ca 2+ overload causes superoxide production and functional impairment, culminating in apoptosis. This vicious cycle of lipotoxicity occurs in multiple tissues, resulting in β-cell failure and insulin resistance in target tissues, and further aggravates diabetic complications.",
author = "Ly, {Luong Dai} and Shanhua Xu and Choi, {Seong Kyung} and Ha, {Chae Myeong} and Themis Thoudam and Cha, {Seung Kuy} and Andreas Wiederkehr and Wollheim, {Claes B.} and Lee, {In Kyu} and Park, {Kyu Sang}",
year = "2017",
month = "2",
day = "3",
doi = "10.1038/emm.2016.143",
language = "English",
volume = "49",
journal = "Experimental and Molecular Medicine",
issn = "1226-3613",
publisher = "Korean Society of Med. Biochemistry and Mol. Biology",
number = "2",

}

Ly, LD, Xu, S, Choi, SK, Ha, CM, Thoudam, T, Cha, SK, Wiederkehr, A, Wollheim, CB, Lee, IK & Park, KS 2017, 'Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes', Experimental and Molecular Medicine, vol. 49, no. 2, e291. https://doi.org/10.1038/emm.2016.143

Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes. / Ly, Luong Dai; Xu, Shanhua; Choi, Seong Kyung; Ha, Chae Myeong; Thoudam, Themis; Cha, Seung Kuy; Wiederkehr, Andreas; Wollheim, Claes B.; Lee, In Kyu; Park, Kyu Sang.

In: Experimental and Molecular Medicine, Vol. 49, No. 2, e291, 03.02.2017.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes

AU - Ly, Luong Dai

AU - Xu, Shanhua

AU - Choi, Seong Kyung

AU - Ha, Chae Myeong

AU - Thoudam, Themis

AU - Cha, Seung Kuy

AU - Wiederkehr, Andreas

AU - Wollheim, Claes B.

AU - Lee, In Kyu

AU - Park, Kyu Sang

PY - 2017/2/3

Y1 - 2017/2/3

N2 - Free fatty acids (FFAs) are important substrates for mitochondrial oxidative metabolism and ATP synthesis but also cause serious stress to various tissues, contributing to the development of metabolic diseases. CD36 is a major mediator of cellular FFA uptake. Inside the cell, saturated FFAs are able to induce the production of cytosolic and mitochondrial reactive oxygen species (ROS), which can be prevented by co-exposure to unsaturated FFAs. There are close connections between oxidative stress and organellar Ca 2+ homeostasis. Highly oxidative conditions induced by palmitate trigger aberrant endoplasmic reticulum (ER) Ca 2+ release and thereby deplete ER Ca 2+ stores. The resulting ER Ca 2+ deficiency impairs chaperones of the protein folding machinery, leading to the accumulation of misfolded proteins. This ER stress may further aggravate oxidative stress by augmenting ER ROS production. Secondary to ER Ca 2+ release, cytosolic and mitochondrial matrix Ca 2+ concentrations can also be altered. In addition, plasmalemmal ion channels operated by ER Ca 2+ depletion mediate persistent Ca 2+ influx, further impairing cytosolic and mitochondrial Ca 2+ homeostasis. Mitochondrial Ca 2+ overload causes superoxide production and functional impairment, culminating in apoptosis. This vicious cycle of lipotoxicity occurs in multiple tissues, resulting in β-cell failure and insulin resistance in target tissues, and further aggravates diabetic complications.

AB - Free fatty acids (FFAs) are important substrates for mitochondrial oxidative metabolism and ATP synthesis but also cause serious stress to various tissues, contributing to the development of metabolic diseases. CD36 is a major mediator of cellular FFA uptake. Inside the cell, saturated FFAs are able to induce the production of cytosolic and mitochondrial reactive oxygen species (ROS), which can be prevented by co-exposure to unsaturated FFAs. There are close connections between oxidative stress and organellar Ca 2+ homeostasis. Highly oxidative conditions induced by palmitate trigger aberrant endoplasmic reticulum (ER) Ca 2+ release and thereby deplete ER Ca 2+ stores. The resulting ER Ca 2+ deficiency impairs chaperones of the protein folding machinery, leading to the accumulation of misfolded proteins. This ER stress may further aggravate oxidative stress by augmenting ER ROS production. Secondary to ER Ca 2+ release, cytosolic and mitochondrial matrix Ca 2+ concentrations can also be altered. In addition, plasmalemmal ion channels operated by ER Ca 2+ depletion mediate persistent Ca 2+ influx, further impairing cytosolic and mitochondrial Ca 2+ homeostasis. Mitochondrial Ca 2+ overload causes superoxide production and functional impairment, culminating in apoptosis. This vicious cycle of lipotoxicity occurs in multiple tissues, resulting in β-cell failure and insulin resistance in target tissues, and further aggravates diabetic complications.

UR - http://www.scopus.com/inward/record.url?scp=85011578616&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85011578616&partnerID=8YFLogxK

U2 - 10.1038/emm.2016.143

DO - 10.1038/emm.2016.143

M3 - Review article

C2 - 28154371

AN - SCOPUS:85011578616

VL - 49

JO - Experimental and Molecular Medicine

JF - Experimental and Molecular Medicine

SN - 1226-3613

IS - 2

M1 - e291

ER -