Ca2+ is a Regulator of the WNK/OSR1/NKCC Pathway in a Human Salivary Gland Cell Line

• 영문명: Ca²⁺ is a Regulator of the WNK/OSR1/NKCC Pathway in a Human Salivary Gland Cell Line
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Soonhong Park Sang Kyun Ku Hye Won Ji Jong-Hoon Choi Dong Min Shin
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제19권 제3호, 249~255쪽, 전체 7쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2015.01.01

영문 초록

Wnk kinase maintains cell volume, regulating various transporters such as sodium-chloride cotransporter, potassium-chloride cotransporter, and sodium-potassium-chloride cotransporter 1 (NKCC1) through the phosphorylation of oxidative stress responsive kinase 1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). However, the activating mechanism of Wnk kinase in specific tissues and specific conditions is broadly unclear. In the present study, we used a human salivary gland (HSG) cell line as a model and showed that Ca²⁺ may have a role in regulating Wnk kinase in the HSG cell line. Through this study, we found that the HSG cell line expressed molecules participating in the WNK-OSR1-NKCC pathway, such as Wnk1, Wnk4, OSR1, SPAK, and NKCC1. The HSG cell line showed an intracellular Ca²⁺ concentration ([Ca²⁺]_i) increase in response to hypotonic stimulation, and the response was synchronized with the phosphorylation of OSR1. Interestingly, when we inhibited the hypotonically induced [Ca²⁺]_i increase with nonspecific Ca²⁺ channel blockers such as 2-aminoethoxydiphenyl borate, gadolinium, and lanthanum, the phosphorylated OSR1 level was also diminished. Moreover, a cyclopiazonic acid-induced passive [Ca²⁺]_i elevation was evoked by the phosphorylation of OSR1, and the amount of phosphorylated OSR1 decreased when the cells were treated with BAPTA, a Ca²⁺ chelator. Finally, through that process, NKCC1 activity also decreased to maintain the cell volume in the HSG cell line. These results indicate that Ca²⁺ may regulate the WNK-OSR1 pathway and NKCC1 activity in the HSG cell line. This is the first demonstration that indicates upstream Ca²⁺ regulation of the WNK-OSR1 pathway in intact cells.

키워드

Ca²⁺ signaling NKCC OSR1 Salivary gland WNK