{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:07:47Z","timestamp":1778598467236,"version":"3.51.4"},"reference-count":41,"publisher":"Portland Press Ltd.","issue":"7","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"vor","delay-in-days":80,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,7,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Premature trypsinogen activation is the early event of acute pancreatitis. Therefore, the studies on the processes of trypsinogen activation induced by compounds are important to understand mechanism underly acute pancreatitis under various conditions. Calcium overload in the early stage of acute pancreatitis was previously found to cause intracellular trypsinogen activation; however, treatment of acute pancreatitis using calcium channel blockers did not produced consistent results. Proteasome activity that could be inhibited by some calcium channel blocker has recently been reported to affect the development of acute pancreatitis; however, the associated mechanism were not fully understood. Here, the roles of nicardipine were investigated in trypsinogen activation in pancreatic acinar cells. The results showed that nicardipine could increase cathepsin B activity that caused trypsinogen activation, but higher concentration of nicardipine or prolonged treatment had an opposite effect. The effects of short time treatment of nicardipine at low concentration were studied here. Proteasome inhibition was observed under nicardipine treatment that contributed to the up-regulation in cytosolic calcium. Increased cytosolic calcium from ER induced by nicardipine resulted in the release and activation of cathepsin B. Meanwhile, calcium chelator inhibited cathepsin B as well as trypsinogen activation. Consistently, proteasome activator protected acinar cells from injury induced by nicardipine. Moreover, proteasome inhibition caused by nicardipine depended on CaMKII. In conclusion, CaMKII down-regulation\/proteasome inhibition\/cytosolic calcium up-regulation\/cathepsin B activation\/trypsinogen activation axis was present in pancreatic acinar cells injury under nicardipine treatment.<\/jats:p>","DOI":"10.1042\/bsr20190516","type":"journal-article","created":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T17:13:59Z","timestamp":1561050839000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["CaMKII\/proteasome\/cytosolic calcium\/cathepsin B axis was present in tryspin activation induced by nicardipine"],"prefix":"10.1042","volume":"39","author":[{"given":"Juan","family":"Xiao","sequence":"first","affiliation":[{"name":"Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Houmin","family":"Lin","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binggang","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, People\u2019s Republic of China"},{"name":"Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9237-9024","authenticated-orcid":false,"given":"Junfei","family":"Jin","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, People\u2019s Republic of China"},{"name":"China-U.S.A. Lipids in Health and Disease Research Center, Guilin Medical University, Guilin 541001, Guangxi, People\u2019s Republic of China"},{"name":"Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin 541001, Guangxi, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2019,7,2]]},"reference":[{"key":"2021111619400602400_B1","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/S0140-6736(95)91695-4","article-title":"Is an elevated concentration of acinar cytosolic free ionised calcium the trigger for acute pancreatitis?","volume":"346","author":"Ward","year":"1995","journal-title":"Lancet"},{"key":"2021111619400602400_B2","first-page":"G352","article-title":"Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats","volume":"275","author":"Hofbauer","year":"1998","journal-title":"Am. J. 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