Mitochondria depletion abolishes agonist-induced Ca2+ plateau in airway smooth muscle cells: potential role of H2O2.
The mechanisms by which mitochondria regulate the sustained phase of agonist-induced responses in cytosolic Ca(2+) concentration as an independent organelle in whole is not clear. By exposing to ethidium bromide and supplying pyruvate and uridine, we established mitochondrial DNA (mtDNA)-depleted rat airway smooth muscle cells (RASMCs) with maintained cellular energy. Upon an exposure to 2 microM histamine, [Ca(2+)](i) in control RASMCs increased to a peak followed by a plateau above baseline, whereas [Ca(2+)](i) in mtDNA-depleted RASMCs jumped to a peak and then declined to baseline without any plateau. mtDNA depletion apparently attenuated intracellular reactive oxygen species generation induced by histamine. By coexposure to 2 microM histamine and 0.1 microM exogenous H(2)O(2), which did not affect [Ca(2+)](i) by itself, the above difference in [Ca(2+)](i) kinetics in mtDNA-depleted RASMCs was reversed. Intracellular H(2)O(2) decomposition abolishes histamine-induced sustained elevation in [Ca(2+)](i) in RASMCs. Thus, mitochondria regulate agonist-induced sustained [Ca(2+)](i) elevation by a H(2)O(2)-dependent mechanism.
Chen
Taoxiang
T
Dept. of Pathophysiology, Tongji Medical College, Huazhong Science and Technology Univ., Wuhan 430030, People's Republic of China.
Zhu
Liping
L
Wang
Tao
T
Ye
Hong
H
Huang
Kewu
K
Hu
Qinghua
Q
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D048430:Cell Shape; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012137:Respiratory System / Q000033:anatomy & histology*; D000071737:Stromal Interaction Molecule 1
D004272:DNA, Mitochondrial; D008562:Membrane Glycoproteins; D016877:Oxidants; D017382:Reactive Oxygen Species; C518857:Stim1 protein, rat; D000071737:Stromal Interaction Molecule 1; D006632:Histamine; D006861:Hydrogen Peroxide; D002118:Calcium