PMID- 31369843
OWN - NLM
STAT- MEDLINE
DCOM- 20200722
LR  - 20200722
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 143
DP  - 2019 Nov 1
TI  - Autophagy protects peripheral blood mononuclear cells against inflammation, 
      oxidative and nitrosative stress in diabetic dyslipidemia.
PG  - 309-323
LID - S0891-5849(19)30706-3 [pii]
LID - 10.1016/j.freeradbiomed.2019.07.034 [doi]
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) results in severe oxidative and 
      nitrosative stress and inflammation when associated with hyperlipidemia. In this 
      study, we have attempted to explore the role of autophagy in T2DM subjects with 
      or without dyslipidemia. METHODS: Experiments were carried out in isolated 
      Peripheral blood mononuclear cells (PBMC) from study subjects and insulin 
      resistant HepG2 cells utilizing flow cytometry, confocal microscopy and molecular 
      biology techniques like western blotting, immunofluorescence and real time PCR. 
      RESULTS: In case of T2DM with dyslipidemia, higher population of autophagy 
      positive cell was detected compared to T2DM which may have been originated due to 
      higher stress. Flow cytometric data indicated autophagy to be triggered by both 
      oxidative and nitrosative stress in PBMC of diabetic dyslipidemic patients, which 
      is a novel finding of our work. Expression of LC3 puncta, a hallmark of autophagy 
      was observed at periphery of PBMC and Hep G2 cells in case of diabetic 
      dyslipidemic condition. Increased expression of ATG5, LC3B and Beclin1 supports 
      the autophagic pathway in both PBMC and Hep G2 cells. Upon blocking autophagy by 
      3-methyl adenine (3MA), the apoptotic cell population increased significantly. 
      Autophagy was also been evidenced to control oxidative stress mediated 
      up-regulation of inflammatory markers like IL-6, TNF-alpha. CONCLUSION: Induction of 
      autophagy emerged to be a protective mechanism for the diabetic cells coupled 
      with dyslipidemia. Not only Reactive oxygen species, but also reactive nitrogen 
      species was involved in autophagy induction process. Moreover inhibition study 
      documented autophagy to have a protective role in pro-inflammatory responses. 
      Thus, enhancing autophagic activity may be an efficient mechanism leading to new 
      therapeutic strategy to restore the glycemic regulation.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Chatterjee, Tanima
AU  - Chatterjee T
AD  - Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, 
      Kolkata, 700019, West Bengal, India.
FAU - Pattanayak, Rudradip
AU  - Pattanayak R
AD  - Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, 
      Kolkata, 700019, West Bengal, India; Jagadis Bose National Science Talent Search, 
      1300, Rajdanga Main Road, Kolkata, 700109, India.
FAU - Ukil, Anindita
AU  - Ukil A
AD  - Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, 
      Kolkata, 700019, West Bengal, India.
FAU - Chowdhury, Subhankar
AU  - Chowdhury S
AD  - Institute of Postgraduate Medical Education and Research, Government of West 
      Bengal, 224, Acharya Jagadish Chandra Bose Road, Kolkata, 700020, India.
FAU - Bhattacharyya, Maitree
AU  - Bhattacharyya M
AD  - Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, 
      Kolkata, 700019, West Bengal, India; Jagadis Bose National Science Talent Search, 
      1300, Rajdanga Main Road, Kolkata, 700109, India. Electronic address: 
      bmaitree@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190729
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Biomarkers)
RN  - 0 (Protective Agents)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Apoptosis
MH  - *Autophagy
MH  - Biomarkers/analysis/metabolism
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/complications/metabolism/pathology/*prevention & 
      control
MH  - Dyslipidemias/complications/metabolism/pathology/*prevention & control
MH  - Female
MH  - Hep G2 Cells
MH  - Humans
MH  - Inflammation/*physiopathology
MH  - Leukocytes, Mononuclear/*immunology/metabolism
MH  - Male
MH  - Middle Aged
MH  - *Nitrosative Stress
MH  - *Oxidative Stress
MH  - Protective Agents
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - Autophagy
OT  - Dyslipidemia
OT  - Reactive nitrogen species
OT  - Reactive oxygen species
OT  - Type 2 diabetes
EDAT- 2019/08/02 06:00
MHDA- 2020/07/23 06:00
CRDT- 2019/08/02 06:00
PHST- 2019/04/26 00:00 [received]
PHST- 2019/06/28 00:00 [revised]
PHST- 2019/07/28 00:00 [accepted]
PHST- 2019/08/02 06:00 [pubmed]
PHST- 2020/07/23 06:00 [medline]
PHST- 2019/08/02 06:00 [entrez]
AID - S0891-5849(19)30706-3 [pii]
AID - 10.1016/j.freeradbiomed.2019.07.034 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2019 Nov 1;143:309-323. doi: 
      10.1016/j.freeradbiomed.2019.07.034. Epub 2019 Jul 29.