PMID- 32033264
OWN - NLM
STAT- MEDLINE
DCOM- 20210329
LR  - 20210329
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 10
IP  - 2
DP  - 2020 Feb 5
TI  - Mitigation of Glucolipotoxicity-Induced Apoptosis, Mitochondrial Dysfunction, and 
      Metabolic Stress by N-Acetyl Cysteine in Pancreatic beta-Cells.
LID - 10.3390/biom10020239 [doi]
LID - 239
AB  - Glucolipotoxicity caused by hyperglycemia and hyperlipidemia are the common 
      features of diabetes-induced complications. Metabolic adaptation, particularly in 
      energy metabolism; mitochondrial dysfunction; and increased inflammatory and 
      oxidative stress responses are considered to be the main characteristics of 
      diabetes and metabolic syndrome. However, due to various fluctuating endogenous 
      and exogenous stimuli, the precise role of these factors under in vivo conditions 
      is not clearly understood. In the present study, we used pancreatic beta-cells, 
      Rin-5F, to elucidate the molecular and metabolic changes in glucolipotoxicity. 
      Cells treated with high glucose (25 mM) and high palmitic acid (up to 0.3 mM) for 
      24 h exhibited increased caspase/poly-ADP ribose polymerase (PARP)-dependent 
      apoptosis followed by DNA fragmentation, alterations in mitochondrial membrane 
      permeability, and bioenergetics, accompanied by alterations in glycolytic and 
      mitochondrial energy metabolism. Our results also demonstrated alterations in the 
      expression of mammalian target of rapamycin (mTOR)/5' adenosine 
      monophosphate-activated protein kinase (AMPK)-dependent apoptotic and autophagy 
      markers. Furthermore, pre-treatment of cells with 10 mM N-acetyl cysteine 
      attenuated the deleterious effects of high glucose and high palmitic acid with 
      improved cellular functions and survival. These results suggest that the presence 
      of high energy metabolites enhance mitochondrial dysfunction and apoptosis by 
      suppressing autophagy and adapting energy metabolism, mediated, at least in part, 
      via enhanced oxidative DNA damage and mTOR/AMPK-dependent cell signaling.
FAU - Alnahdi, Arwa
AU  - Alnahdi A
AD  - Department of Biochemistry, College of Medicine and Health Sciences, United Arab 
      Emirates University, P.O. Box 17666, Al Ain, UAE.
FAU - John, Annie
AU  - John A
AD  - Department of Biochemistry, College of Medicine and Health Sciences, United Arab 
      Emirates University, P.O. Box 17666, Al Ain, UAE.
FAU - Raza, Haider
AU  - Raza H
AD  - Department of Biochemistry, College of Medicine and Health Sciences, United Arab 
      Emirates University, P.O. Box 17666, Al Ain, UAE.
LA  - eng
GR  - HR-31M377; MRG-18/2013-2014/This research was funded by the Sheikh Hamdan Medical 
      Research Award () and the Research Committee, College of Medicine and Health 
      Sciences, UAE University, Al Ain, UAE (HR- 31M377)./International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200205
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Fatty Acids)
RN  - 0 (Reactive Oxygen Species)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - IY9XDZ35W2 (Glucose)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*metabolism
MH  - Animals
MH  - *Apoptosis
MH  - Autophagy/drug effects
MH  - Cell Line
MH  - DNA Damage
MH  - DNA Fragmentation
MH  - Fatty Acids/metabolism
MH  - Glucose/*pharmacology
MH  - Inflammation
MH  - Insulin-Secreting Cells/*metabolism
MH  - Membrane Potential, Mitochondrial
MH  - Mitochondria/*metabolism
MH  - Oxidation-Reduction
MH  - Oxidative Stress
MH  - Palmitic Acid/pharmacology
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
PMC - PMC7072690
OTO - NOTNLM
OT  - Rin-5F cells
OT  - apoptosis
OT  - autophagy
OT  - glucolipotoxicity
OT  - mitochondrial dysfunction
OT  - palmitic acid
COIS- The authors declare no conflict of interest.
EDAT- 2020/02/09 06:00
MHDA- 2021/03/30 06:00
PMCR- 2020/02/01
CRDT- 2020/02/09 06:00
PHST- 2019/12/05 00:00 [received]
PHST- 2020/01/19 00:00 [revised]
PHST- 2020/01/24 00:00 [accepted]
PHST- 2020/02/09 06:00 [entrez]
PHST- 2020/02/09 06:00 [pubmed]
PHST- 2021/03/30 06:00 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
AID - biom10020239 [pii]
AID - biomolecules-10-00239 [pii]
AID - 10.3390/biom10020239 [doi]
PST - epublish
SO  - Biomolecules. 2020 Feb 5;10(2):239. doi: 10.3390/biom10020239.