Volatile anesthetics, calcium homeostasis and apoptosis

挥发性麻醉剂、钙稳态和细胞凋亡

• 批准号: 7596179
• 负责人: HUAFENG WEI
• 金额: $ 12.79万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7596179
• 关键词: Affect; Aftercare; Age; Agonist; Alzheimer' s Disease; Anesthesiology; Anesthetics; Animals; Apoptosis; Awareness; Basic Science; Bax protein; Behavioral; Ca(2+)-Transporting ATPase; Calcium; Cell Survival; Cell model; Cells; Cognition; Commit; Data; Dose; Dyes; Endoplasmic Reticulum; Exposure to; Fura-2; General Anesthesia; General anesthetic drugs; Goals; Hippocampus (Brain); Histopathology; Homeostasis; Image; Impaired cognition; In Situ Nick-End Labeling; In Vitro; Investigation; Isoflurane; Learning; Maintenance; Microsomes; Modeling; Muscle; Nerve Degeneration; Neurons; PC12 Cells; Patient Care; Pennsylvania; Physicians; Play; Protein Family; Rattus; Research Project Grants; Role; Ryanodine; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; Sarcoplasmic Reticulum; Scientist; System; Testing; Time; Training; Universities; base; career; cognitive function; cytotoxicity; improved; in vivo; inhibitor/antagonist; neuron apoptosis; professor; receptor; reuptake; sevoflurane

DESCRIPTION (provided by applicant): As an anesthesiologist, the applicant is firmly committed to advancing academic anesthesiology through basic research. His ultimate career goal is to improve peri-operative patient care, and his immediate career goal is to create more effective and safer general anesthetics. As an assistant professor in the tenure track, Dr. Wei will receive excellent training at the University of Pennsylvania. This proposal will complete his training and provide the initial transition to becoming an independent physician-scientist. Volatile genearal anesthetics are the most common agents used for maintenance of general anesthesia, but the increasing awareness of their long lasting effects on cognition and learning suggests enhanced neurodegeneration. The overall goal of this research project is to understand whether disruption of calcium homeostasis by volatile anesthetics leads to apoptosis. The immediate goal of the study is to investigate if isoflurane and sevoflurane interact with calcium homeostasis in the endoplasmic reticulum (ER) differently, thus contributing to neuronal apoptosis in different ways. The central hypothesis is that isoflurane, but not sevoflurane, induces neuronal apoptosis via depletion of calcium in the ER. We will test several sub hypotheses via the following specific aims: (1). Aim 1 will test that isoflurane, but not sevoflurane, induces apoptosis in both normal neurons and in a cell model of Alzheimer's disease because of its existing disruption of ER calcium. (2). Aim 2 will test the hypothesis that Isoflurane depletes, but sevoflurane maintains or increases, ER calcium contents. (3). Aim 3 will investigate if isoflurane and sevoflurane change the apoptosis-related Bcl-2 family proteins differently in cells. (4). Aim 4 will test the hypothesis that Isoflurane, but not sevoflurane, decreases the Bcl-2/Bax ratio, causing neuronal degeneration at different ages, resulting in learning deficits and/or cognitive dysfunction in the rat. We will examine neuronal apoptosis by histopathology, and learning and cognition change in animals after treatment of isoflurane or sevoflurane.

描述（由申请人提供）：作为一名麻醉师，申请人坚定地致力于通过基础研究推动麻醉学的学术发展。他的最终职业目标是改善围手术期患者护理，他的近期职业目标是创造更有效、更安全的全麻药。作为终身教授的助理教授，魏博士将在宾夕法尼亚大学接受优秀的培训。这一建议将完成他的培训，并为他成为一名独立的内科科学家提供初步过渡。

项目成果

The common inhaled anesthetic isoflurane increases aggregation of huntingtin and alters calcium homeostasis in a cell model of Huntington's disease.

• DOI: 10.1016/j.taap.2010.10.032
• 发表时间: 2011-02-01
• 期刊: Toxicology and applied pharmacology
• 影响因子: 3.8
• 作者: Wang Q;Liang G;Yang H;Wang S;Eckenhoff MF;Wei H
• 通讯作者: Wei H

General Anesthetics Regulate Autophagy via Modulating the Inositol 1,4,5-Trisphosphate Receptor: Implications for Dual Effects of Cytoprotection and Cytotoxicity.

• DOI: 10.1038/s41598-017-11607-0
• 发表时间: 2017-09-28
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Ren G;Zhou Y;Liang G;Yang B;Yang M;King A;Wei H
• 通讯作者: Wei H

Propofol Affects Neurodegeneration and Neurogenesis by Regulation of Autophagy via Effects on Intracellular Calcium Homeostasis.

• DOI: 10.1097/aln.0000000000001730
• 发表时间: 2017-09
• 期刊: Anesthesiology
• 影响因子: 8.8
• 作者: Qiao H;Li Y;Xu Z;Li W;Fu Z;Wang Y;King A;Wei H
• 通讯作者: Wei H

Dual effects of isoflurane on proliferation, differentiation, and survival in human neuroprogenitor cells.

• DOI: 10.1097/aln.0b013e3182833fae
• 发表时间: 2013-03
• 期刊: Anesthesiology
• 影响因子: 8.8
• 作者: Zhao X;Yang Z;Liang G;Wu Z;Peng Y;Joseph DJ;Inan S;Wei H
• 通讯作者: Wei H

S100β in newborns after C-section with general vs. epidural anesthesia: a prospective observational study.

• DOI: 10.1111/aas.13038
• 发表时间: 2018-03
• 期刊: Acta anaesthesiologica Scandinavica
• 影响因子: 2.1
• 作者: Xu Z;Liu Z;Zhang Y;Jin C;Shen F;Yu Y;Cheek T;Onuoha O;Liang G;Month R;Atkins J;Tran KM;Wei H
• 通讯作者: Wei H