PMID- 27586872
OWN - NLM
STAT- MEDLINE
DCOM- 20170504
LR  - 20170504
IS  - 1873-3468 (Electronic)
IS  - 0014-5793 (Linking)
VI  - 590
IP  - 19
DP  - 2016 Oct
TI  - Homocysteine augments BK channel activity and decreases exocytosis of secretory 
      granules in rat GH3 cells.
PG  - 3375-3384
LID - 10.1002/1873-3468.12381 [doi]
AB  - In this study, we investigated the effects of L-homocysteine (Hcy) on maxi 
      calcium-activated potassium (BK) channels and on exocytosis of secretory granules 
      in GH3 rat pituitary-derived cells. A major finding of our study indicates that 
      short-term application of Hcy increased the open probability of oxidized BK 
      channels in inside-out recordings. Whole-cell recordings show that extracellular 
      Hcy also augmented BK currents during long-term application. Furthermore, Hcy 
      decreased the exocytosis of secretory granules. This decrease was partially 
      prevented by the BK channel inhibitor paxilline and fully prevented by 
      N-acetylcysteine, a reactive oxygen species scavenger. Taken together, our data 
      show that elevation of cellular Hcy level induces oxidative stress, increases BK 
      channel activity, and decreases exocytosis of secretory granules. These findings 
      may provide insight into some of the developmental impairments and neurotoxicity 
      associated with Hyperhomocysteinemia (HHcy), a disease arising due to abnormally 
      elevated levels of Hcy in the plasma.
CI  - (c) 2016 Federation of European Biochemical Societies.
FAU - Gaifullina, Aisylu S
AU  - Gaifullina AS
AD  - Department of Human and Animal Physiology, Institute of Fundamental Medicine and 
      Biology, Kazan Federal University, Russia.
FAU - Yakovlev, Aleksey V
AU  - Yakovlev AV
AD  - Department of Human and Animal Physiology, Institute of Fundamental Medicine and 
      Biology, Kazan Federal University, Russia.
FAU - Mustafina, Alsu N
AU  - Mustafina AN
AD  - Department of Human and Animal Physiology, Institute of Fundamental Medicine and 
      Biology, Kazan Federal University, Russia.
FAU - Weiger, Thomas M
AU  - Weiger TM
AD  - Department of Cell Biology and Physiology, University of Salzburg, Austria.
FAU - Hermann, Anton
AU  - Hermann A
AD  - Department of Cell Biology and Physiology, University of Salzburg, Austria.
FAU - Sitdikova, Guzel F
AU  - Sitdikova GF
AD  - Department of Human and Animal Physiology, Institute of Fundamental Medicine and 
      Biology, Kazan Federal University, Russia. sitdikovaguzel@gmail.com.
LA  - eng
PT  - Letter
DEP - 20160915
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Indoles)
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (Potassium Channel Blockers)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 3T9U9Z96L7 (paxilline)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Action Potentials/drug effects
MH  - Animals
MH  - Cell Line
MH  - Exocytosis/*drug effects
MH  - Homocysteine/*pharmacology
MH  - Indoles/pharmacology
MH  - Large-Conductance Calcium-Activated Potassium Channels/*metabolism
MH  - Potassium Channel Blockers/pharmacology
MH  - Rats
MH  - Secretory Vesicles/*drug effects/metabolism
OTO - NOTNLM
OT  - BK channels
OT  - exocytosis
OT  - homocysteine
OT  - oxidative stress
EDAT- 2016/09/03 06:00
MHDA- 2017/05/05 06:00
CRDT- 2016/09/03 06:00
PHST- 2016/06/30 00:00 [received]
PHST- 2016/08/22 00:00 [revised]
PHST- 2016/08/28 00:00 [accepted]
PHST- 2016/09/03 06:00 [pubmed]
PHST- 2017/05/05 06:00 [medline]
PHST- 2016/09/03 06:00 [entrez]
AID - 10.1002/1873-3468.12381 [doi]
PST - ppublish
SO  - FEBS Lett. 2016 Oct;590(19):3375-3384. doi: 10.1002/1873-3468.12381. Epub 2016 
      Sep 15.