PMID- 25481834
OWN - NLM
STAT- MEDLINE
DCOM- 20150916
LR  - 20191210
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1852
IP  - 3
DP  - 2015 Mar
TI  - TNF-alpha regulates miRNA targeting mitochondrial complex-I and induces cell death in 
      dopaminergic cells.
PG  - 451-61
LID - S0925-4439(14)00361-5 [pii]
LID - 10.1016/j.bbadis.2014.11.019 [doi]
AB  - Parkinson's disease (PD) is a complex neurological disorder of the elderly 
      population and majorly shows the selective loss of dopaminergic (DAergic) neurons 
      in the substantia nigra pars compacta (SNpc) region of the brain. The mechanisms 
      leading to increased cell death of DAergic neurons are not well understood. Tumor 
      necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine is elevated in blood, 
      CSF and striatum region of the brain in PD patients. The increased level of TNF-alpha 
      and its role in pathogenesis of PD are not well understood. In the current study, 
      we investigated the role of TNF-alpha in the regulation of cell death and miRNA 
      mediated mitochondrial functions using, DAergic cell line, SH-SY5Y (model of 
      dopaminergic neuron degeneration akin to PD). The cells treated with low dose of 
      TNF-alpha for prolonged period induce cell death which was rescued in the presence of 
      zVAD.fmk, a caspase inhibitor and N-acetyl-cysteine (NAC), an antioxidant. TNF-alpha 
      alters mitochondrial complex-I activity, decreases adenosine triphosphate (ATP) 
      levels, increases reactive oxygen species levels and mitochondrial turnover 
      through autophagy. TNF-alpha differentially regulates miRNA expression involved in 
      pathogenesis of PD. Bioinformatics analysis revealed that the putative targets of 
      altered miRNA included both pro/anti apoptotic genes and subunits of 
      mitochondrial complex. The cells treated with TNF-alpha showed decreased level of 
      nuclear encoded transcript of mitochondrial complexes, the target of miRNA. To 
      our knowledge, the evidences in the current study demonstrated that TNF-alpha is a 
      potential regulator of miRNAs which may regulate mitochondrial functions and 
      neuronal cell death, having important implication in pathogenesis of PD.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Prajapati, Paresh
AU  - Prajapati P
AD  - Department of Cell Biology, School of Biological Sciences and Biotechnology, 
      Indian Institute of Advanced Research (IIAR), Koba Institutional Area, 
      Gandhinagar 382007, Gujarat, India; Department of Biochemistry, Faculty of 
      Science, The M. S. University of Baroda, Vadodara 390002, Gujarat, India.
FAU - Sripada, Lakshmi
AU  - Sripada L
AD  - Department of Cell Biology, School of Biological Sciences and Biotechnology, 
      Indian Institute of Advanced Research (IIAR), Koba Institutional Area, 
      Gandhinagar 382007, Gujarat, India; Department of Biochemistry, Faculty of 
      Science, The M. S. University of Baroda, Vadodara 390002, Gujarat, India.
FAU - Singh, Kritarth
AU  - Singh K
AD  - Department of Cell Biology, School of Biological Sciences and Biotechnology, 
      Indian Institute of Advanced Research (IIAR), Koba Institutional Area, 
      Gandhinagar 382007, Gujarat, India; Department of Biochemistry, Faculty of 
      Science, The M. S. University of Baroda, Vadodara 390002, Gujarat, India.
FAU - Bhatelia, Khyati
AU  - Bhatelia K
AD  - Department of Cell Biology, School of Biological Sciences and Biotechnology, 
      Indian Institute of Advanced Research (IIAR), Koba Institutional Area, 
      Gandhinagar 382007, Gujarat, India; Department of Biochemistry, Faculty of 
      Science, The M. S. University of Baroda, Vadodara 390002, Gujarat, India.
FAU - Singh, Rochika
AU  - Singh R
AD  - Department of Cell Biology, School of Biological Sciences and Biotechnology, 
      Indian Institute of Advanced Research (IIAR), Koba Institutional Area, 
      Gandhinagar 382007, Gujarat, India.
FAU - Singh, Rajesh
AU  - Singh R
AD  - Department of Biochemistry, Faculty of Science, The M. S. University of Baroda, 
      Vadodara 390002, Gujarat, India. Electronic address: singhraj1975@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141204
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (MicroRNAs)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (benzyloxycarbonyl-valyl-aspartic acid fluoromethyl ketone)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Adenosine Triphosphate/metabolism
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Cell Death/drug effects
MH  - Cell Line
MH  - Dopaminergic Neurons/*enzymology/pathology
MH  - Electron Transport Complex I/*metabolism
MH  - Free Radical Scavengers/pharmacology
MH  - Humans
MH  - MicroRNAs/*metabolism
MH  - Mitochondria/*enzymology/pathology
MH  - Parkinson Disease/*enzymology/pathology
MH  - Protease Inhibitors/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
OTO - NOTNLM
OT  - Inflammation
OT  - Mitochondria
OT  - Parkinson's disease
OT  - TNF-alpha
OT  - miRNA
EDAT- 2014/12/08 06:00
MHDA- 2015/09/17 06:00
CRDT- 2014/12/08 06:00
PHST- 2014/09/01 00:00 [received]
PHST- 2014/11/22 00:00 [revised]
PHST- 2014/11/26 00:00 [accepted]
PHST- 2014/12/08 06:00 [entrez]
PHST- 2014/12/08 06:00 [pubmed]
PHST- 2015/09/17 06:00 [medline]
AID - S0925-4439(14)00361-5 [pii]
AID - 10.1016/j.bbadis.2014.11.019 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2015 Mar;1852(3):451-61. doi: 10.1016/j.bbadis.2014.11.019. 
      Epub 2014 Dec 4.