- 作者: Fang-hao Lu; Zhiliang Tian; Wei-hua Zhang; Ya-jun Zhao; Hu-lun Li; Huan Ren; Hui-shuang Zheng; Chong Liu; Guang-xia Hu; Ye Tian; Bao-feng Yang; Rui Wang; Chang-qing Xu
- 作者服務機構: Department of Pathophysiology, Harbin Medical University, Harbin, China
- 中文摘要: --
- 英文摘要:
Communication between the SR (sarcoplasmic reticulum, SR) and mitochondria is
important for cell survival and apoptosis. The SR supplies Ca2+ directly to
mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts
between the two organelles referred to as mitochondrion-associated ER membrane
(MAM). Although it has been demonstrated that CaR (calcium sensing receptor)
activation is involved in intracellular calcium overload during hypoxia/reoxygenation
(H/Re), the role of CaR activation in the cardiomyocyte apoptotic pathway remains
unclear. We postulated that CaR activation plays a role in the regulation of
SR-mitochondrial inter-organelle Ca2+ signaling, causing apoptosis during H/Re. To
investigate the above hypothesis, cultured cardiomyocytes were subjected to H/Re.
We examined the distribution of IP3Rs in cardiomyocytes via immunofluorescence
and Western blotting and found that type 3 IP3Rs were located in the SR. [Ca2+]i,
[Ca2+]m and [Ca2+]SR were determined using Fluo-4, x-rhod-1 and Fluo 5N,
respectively, and the mitochondrial membrane potential was detected with JC-1
during reoxygenation using laser confocal microscopy. We found that activation of
CaR reduced [Ca2+]SR, increased [Ca2+]i and [Ca2+]m and decreased the mitochondrial
membrane potential during reoxygenation. We found that the activation of CaR
caused the cleavage of BAP31, thus generating the pro-apoptotic p20 fragment, which
induced the release of cytochrome c from mitochondria and the translocation of
bak/bax to mitochondria. Taken together, these results reveal that CaR activation
causes Ca2+ release from the SR into the mitochondria through IP3Rs and induces
cardiomyocyte apoptosis during hypoxia/reoxygenation. - 中文關鍵字: --
- 英文關鍵字: --