The Effects of DTBNP on Intracellular Ca2+ Signaling in Cultured Bovine Aortic Endothelial Cells

• 영문명: The Effects of DTBNP on Intracellular Ca²⁺ Signaling in Cultured Bovine Aortic Endothelial Cells
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Sung Jin Park Byung Joo Kim Mei Hong Zhu Insuk So Ki Whan Kim
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제9권 제6호, 341~346쪽, 전체 6쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2005.01.01

영문 초록

The mechanism underlying oxidant-induced intracellular Ca²⁺ ([Ca²⁺]_i) increase was studied in cultured bovine aortic endothelial cells (BAECs) using fura-2 AM. In the presence of 2 mM extracellular Ca²⁺, the application of DTBNP (20μM), a membrane-permeable oxidant, caused an increase in [Ca²⁺]_i, and DTT (2 mM) as a reductant completely reversed the effect of DTBNP. The [Ca²⁺]_i increase induced by DTBNP was also observed in an extracellular Ca²⁺-free/2 mM EGTA solution, indicating the release of Ca²⁺ from intracellular store(s). After endoplasmic reticulum was depleted by an IP₃-generating agonist, ATP (30μM) or an ER Ca²⁺ pump inhibitor, thapsigargin (1μM), DTBNP-stressed BAECs showed an increase of [Ca²⁺]_i in Ca²⁺-free/2 mM EGTA solution. Ratio-differences before and after the application of DTBNP after pretreatment with ATP or thapsigargin were 0.42⁑0.15 and 0.49⁑0.07, respectively (n=7), which are significantly reduced, compared to the control value of 0.72⁑0.07 in a Ca²⁺-free/2 mM EGTA solution. After the protonophore CCCP (10μM) challenge to release mitochondrial Ca²⁺, the similar result was obtained. Ratio-difference before and after the application of DTBNP after pretreatment with CCCP was 0.46⁑0.09 (n=7). Simultaneous application of thapsigargin and CCCP completely abolished the DTBNP-induced [Ca²⁺]_i increase. The above results together indicate that the increase of [Ca²⁺]_i by DTBNP resulted from the release of Ca²⁺ from both endoplasmic reticulum and mitochondria.

키워드

Oxidant DTBNP DTT Bovine aortic endothelial cells Endoplasmic reticulum Mitochondria