PMID- 30666538
OWN - NLM
STAT- MEDLINE
DCOM- 20190830
LR  - 20190830
IS  - 1432-0878 (Electronic)
IS  - 0302-766X (Linking)
VI  - 376
IP  - 2
DP  - 2019 May
TI  - Oxidative stress modulates the expression of apoptosis-associated microRNAs in 
      bovine granulosa cells in vitro.
PG  - 295-308
LID - 10.1007/s00441-019-02990-3 [doi]
AB  - Despite its essential role in ovulation, oxidative stress (OS) has been found to 
      be cytotoxic to cells, while microRNAs (miRNAs) are known as a major regulator of 
      genes involved in cellular defense against cytotoxicity. However, a functional 
      link between OS and miRNA expression changes in granulosa cells (GCs) remains to 
      be investigated. Here, we investigate the OS modulation of apoptosis-associated 
      miRNAs and their biological relevance in bovine GCs. Following the evaluation of 
      cell viability, accumulation of reactive oxygen species (ROS), cytotoxicity and 
      mitochondrial activity, we used a ready-to-use miRNA PCR array to identify 
      differentially regulated miRNAs. The results showed that exposure to 150 muM 
      H(2)O(2) for 4 h creates remarkable signs of OS in GCs characterized by more than 
      50% loss of cell viability, higher nuclear factor erythroid 2-related factor 2 
      (NRF2) nuclear translocation, significantly (p < 0.05) higher abundance of 
      antioxidant genes, significantly (p < 0.001) higher accumulation of ROS, lower 
      mitochondrial activity and a higher (p < 0.001) number of apoptotic nuclei 
      compared to that of the control group. miRNA expression analysis revealed that a 
      total of 69 miRNAs were differentially regulated in which 47 and 22 miRNAs were 
      up- and downregulated, respectively, in stressed GCs. By applying the 2-fold and 
      p < 0.05 criteria, we found 16 miRNAs were upregulated and 10 miRNAs were 
      downregulated. Target prediction revealed that up- and downregulated miRNAs 
      potentially targeted a total of 6210 and 3575 genes, respectively. Pathway 
      analysis showed that upregulated miRNAs are targeting the genes involved mostly 
      in cell survival, intracellular communication and homeostasis, cellular migration 
      and growth control and disease pathways. Our results showed that OS modulates the 
      expression of apoptosis-associated miRNAs that might have effects on cellular or 
      molecular damages.
FAU - Sohel, Md Mahmodul Hasan
AU  - Sohel MMH
AD  - Genome and Stem Cell Centre, Erciyes University, 38039, Kayseri, Turkey. 
      sohel@erciyes.edu.tr.
AD  - Department of Animal Science, Faculty of Agriculture, Erciyes University, 38039, 
      Kayseri, Turkey. sohel@erciyes.edu.tr.
FAU - Akyuz, Bilal
AU  - Akyuz B
AD  - Department of Genetics, Faculty of Veterinary Science, Erciyes University, 38039, 
      Kayseri, Turkey.
FAU - Konca, Yusuf
AU  - Konca Y
AD  - Department of Animal Science, Faculty of Agriculture, Erciyes University, 38039, 
      Kayseri, Turkey.
FAU - Arslan, Korhan
AU  - Arslan K
AD  - Department of Genetics, Faculty of Veterinary Science, Erciyes University, 38039, 
      Kayseri, Turkey.
FAU - Sariozkan, Serpil
AU  - Sariozkan S
AD  - Department of Fertility and Artificial Insemination, Faculty of Veterinary 
      Science, Erciyes University, 38039, Kayseri, Turkey.
FAU - Cinar, Mehmet Ulas
AU  - Cinar MU
AD  - Department of Animal Science, Faculty of Agriculture, Erciyes University, 38039, 
      Kayseri, Turkey.
LA  - eng
GR  - FOA-2015-5655/Erciyes University Scientific Research Projects Coordination Unit/
PT  - Journal Article
DEP - 20190121
PL  - Germany
TA  - Cell Tissue Res
JT  - Cell and tissue research
JID - 0417625
RN  - 0 (MicroRNAs)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Reactive Oxygen Species)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cattle
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Down-Regulation
MH  - Female
MH  - Gene Expression Profiling
MH  - Granulosa Cells/cytology/*metabolism
MH  - Hydrogen Peroxide/chemistry
MH  - MicroRNAs/genetics/*metabolism
MH  - Mitochondria/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - *Oxidative Stress
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - Up-Regulation
OTO - NOTNLM
OT  - Apoptosis
OT  - Granulosa cells
OT  - Oxidative stress
OT  - Signaling pathways
OT  - microRNA
EDAT- 2019/01/23 06:00
MHDA- 2019/08/31 06:00
CRDT- 2019/01/23 06:00
PHST- 2018/03/07 00:00 [received]
PHST- 2019/01/02 00:00 [accepted]
PHST- 2019/01/23 06:00 [pubmed]
PHST- 2019/08/31 06:00 [medline]
PHST- 2019/01/23 06:00 [entrez]
AID - 10.1007/s00441-019-02990-3 [pii]
AID - 10.1007/s00441-019-02990-3 [doi]
PST - ppublish
SO  - Cell Tissue Res. 2019 May;376(2):295-308. doi: 10.1007/s00441-019-02990-3. Epub 
      2019 Jan 21.