PMID- 27778132
OWN - NLM
STAT- MEDLINE
DCOM- 20180212
LR  - 20211204
IS  - 1573-675X (Electronic)
IS  - 1360-8185 (Linking)
VI  - 22
IP  - 1
DP  - 2017 Jan
TI  - Insights on the involvement of (-)-epigallocatechin gallate in ER stress-mediated 
      apoptosis in age-related macular degeneration.
PG  - 72-85
LID - 10.1007/s10495-016-1318-2 [doi]
AB  - Endoplasmic reticulum (ER) stress-mediated apoptosis is a well-known factor in 
      the pathogenesis of age-related macular degeneration (AMD). ER stress leads to 
      accumulation of misfolded proteins, which in turn activates unfolded protein 
      response (UPR) of the cell for its survival. The prolonged UPR of ER stress 
      promotes cell death; however, the transition between adaptation and ER 
      stress-induced apoptosis has not been clearly understood. Hence, the present 
      study investigates the regulatory effect of (-)-epigallocatechin gallate (EGCG) 
      on ER stress-induced by hydrogen peroxide (H(2)O(2)) and disturbance of calcium 
      homeostasis by thapsigargin (TG) in mouse retinal pigment epithelial (MRPE) 
      cells. The oxidant molecules influenced MRPE cells showed an increased level of 
      intracellular calcium [Ca(2+)](i) in ER and transferred to mitochondria through 
      ER-mitochondrial tether site then increased ROS production. EGCG restores 
      [Ca(2+)](i) homeostasis by decreasing ROS production through inhibition of 
      prohibitin1 which regulate ER-mitochondrial tether site and inhibit apoptosis. 
      Effect of EGCG on ER stress-mediated apoptosis was elucidated by exploring the 
      UPR signalling pathways. EGCG downregulated GRP78, CHOP, PERK, ERO1alpha, IRE1alpha, 
      cleaved PARP, cleaved caspase 3, caspase 12 and upregulated expression of 
      calnexinin MRPE cells. In addition to this, inhibition of apoptosis by EGCG was 
      also confirmed with expression of proteins Akt, PTEN and GSK3beta. MRPE cells with 
      EGCG upregulates phosphorylation of Akt at ser473 and phospho ser380 of PTEN, but 
      phosphorylation at ser9 of GSK3beta was inhibited. Further, constitutively active 
      (myristoylated) CA-Akt transfected in MRPE cells had an increased Akt activity in 
      EGCG influenced cells. These findings strongly suggest that antioxidant molecules 
      inhibit cell death through the proper balancing of [Ca(2+)](i) and ROS production 
      in order to maintain UPR of ER in MRPE cells. Thus, modulation of UPR signalling 
      may provide a potential target for the therapeutic approaches of AMD.
FAU - Karthikeyan, Bose
AU  - Karthikeyan B
AD  - Department of Biotechnology, Kalasalingam University, Anand Nagar, Krishnankoil, 
      Tamil Nadu, 626 126, India.
AD  - Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, 
      Cleveland, OH, 44195, USA.
FAU - Harini, Lakshminarasimhan
AU  - Harini L
AD  - Department of Biotechnology, Kalasalingam University, Anand Nagar, Krishnankoil, 
      Tamil Nadu, 626 126, India.
FAU - Krishnakumar, Vaithilingam
AU  - Krishnakumar V
AD  - Department of Microbiology, Bharathidasan University, Tiruchirappalli, Tamil 
      Nadu, 620 024, India.
FAU - Kannan, Velu Rajesh
AU  - Kannan VR
AD  - Department of Microbiology, Bharathidasan University, Tiruchirappalli, Tamil 
      Nadu, 620 024, India.
FAU - Sundar, Krishnan
AU  - Sundar K
AD  - Department of Biotechnology, Kalasalingam University, Anand Nagar, Krishnankoil, 
      Tamil Nadu, 626 126, India.
AD  - International Research Centre, Kalasalingam University, Krishnankoil, Tamil Nadu, 
      626 126, India.
FAU - Kathiresan, Thandavarayan
AU  - Kathiresan T
AD  - Department of Biotechnology, Kalasalingam University, Anand Nagar, Krishnankoil, 
      Tamil Nadu, 626 126, India. t.kathiresan@klu.ac.in.
AD  - International Research Centre, Kalasalingam University, Krishnankoil, Tamil Nadu, 
      626 126, India. t.kathiresan@klu.ac.in.
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (Antioxidants)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Hspa5 protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - 67526-95-8 (Thapsigargin)
RN  - 8R1V1STN48 (Catechin)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Apoptosis/*drug effects
MH  - Calcium/metabolism
MH  - Calcium Signaling/genetics
MH  - Catechin/administration & dosage/*analogs & derivatives
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*drug effects/genetics
MH  - Humans
MH  - Hydrogen Peroxide/toxicity
MH  - Macular Degeneration/*drug therapy/genetics
MH  - Mice
MH  - Mitochondria/drug effects/genetics
MH  - Oxidative Stress/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Thapsigargin/administration & dosage
MH  - Unfolded Protein Response/drug effects/*genetics
OTO - NOTNLM
OT  - AMD
OT  - Akt
OT  - Caspase
OT  - EGCG
OT  - ER-mitochondrial tether site
OT  - Intracellular calcium
OT  - ROS
EDAT- 2016/10/26 06:00
MHDA- 2018/02/13 06:00
CRDT- 2016/10/26 06:00
PHST- 2016/10/26 06:00 [pubmed]
PHST- 2018/02/13 06:00 [medline]
PHST- 2016/10/26 06:00 [entrez]
AID - 10.1007/s10495-016-1318-2 [pii]
AID - 10.1007/s10495-016-1318-2 [doi]
PST - ppublish
SO  - Apoptosis. 2017 Jan;22(1):72-85. doi: 10.1007/s10495-016-1318-2.