N-acetyl-L-cysteine and cysteine increase intracellular calcium concentration in human neutrophils.
10.4196/kjpp.2016.20.5.449
- Author:
Md Ashraful HASAN
1
;
Won Gyun AHN
;
Dong Keun SONG
Author Information
1. Department of Pharmacology, College of Medicine, Hallym University, Chuncheon 24252, Korea. dksong@hallym.ac.kr
- Publication Type:Original Article
- Keywords:
Acetyl-L-cysteine;
Cysteine;
Human neutrophils;
Intracellular free-calcium concentration
- MeSH:
Acetylcysteine*;
Calcium Channels;
Calcium*;
Cysteine*;
HEPES;
Humans*;
Neutrophils*;
Ruthenium;
Ruthenium Red
- From:The Korean Journal of Physiology and Pharmacology
2016;20(5):449-457
- CountryRepublic of Korea
- Language:English
-
Abstract:
N-acetyl-L-cysteine (NAC) and cysteine have been implicated in a number of human neutrophils' functional responses. However, though Ca²⁺ signaling is one of the key signalings contributing to the functional responses of human neutrophils, effects of NAC and cysteine on intracellular calcium concentration ([Ca²⁺]ᵢ) in human neutrophils have not been investigated yet. Thus, this study was carried out with an objective to investigate the effects of NAC and cysteine on [Ca²⁺]ᵢ in human neutrophils. We observed that NAC (1 µM ~ 1 mM) and cysteine (10 µM ~ 1 mM) increased [Ca²⁺]ᵢ in human neutrophils in a concentration-dependent manner. In NAC pre-supplmented buffer, an additive effect on N-formyl-methionine-leucine-phenylalanine (fMLP)-induced increase in [Ca²⁺]ᵢ in human neutrophils was observed. In Ca²⁺-free buffer, NAC- and cysteine-induced [Ca²⁺]ᵢ increase in human neutrophils completely disappeared, suggesting that NAC- and cysteine-mediated increase in [Ca²⁺]ᵢ in human neutrophils occur through Ca²⁺ influx. NAC- and cysteine-induced [Ca²⁺]ᵢ increase was effectively inhibited by calcium channel inhibitors SKF96365 (10 µM) and ruthenium red (20 µM). In Na⁺-free HEPES, both NAC and cysteine induced a marked increase in [Ca²⁺]ᵢ in human neutrophils, arguing against the possibility that Na⁺-dependent intracellular uptake of NAC and cysteine is necessary for their [Ca²⁺]ᵢ increasing activity. Our results show that NAC and cysteine induce [Ca²⁺]ᵢ increase through Ca²⁺ influx in human neutrophils via SKF96365- and ruthenium red-dependent way.