PICK1 deficiency exacerbates sepsis-associated acute lung injury and impairs glutathione synthesis via reduction of xCT

Free Radical Biology & Medicine
Meizi QianJun Lu Wang

Abstract

The role of oxidative stress has been well documented in the development of sepsis-induced acute lung injury (ALI). Protein interaction with C-kinase 1 (PICK1) participates in oxidative stress-related neuronal diseases. However, its function in lung infections and inflammatory diseases is not known. We therefore sought to investigate whether PICK1 is involved in sepsis-induced ALI. Cecal ligation and puncture (CLP) was performed in anesthetized wild type (WT) and PICK1 knock out (KO, PICK1-/-) mice with C57BL/6 background. At the time of CLP, mice were given fluid resuscitation. Mouse lungs were harvested at 24 and 72 h for Western blot analysis, qRT-PCR, BALF analysis, Hematoxylin and Eosin staining, TUNEL staining, maleimide staining, flow cytometry analysis, GCL, GSH, GSSG and cysteine levels measurement. A marked elevation of PICK1 mRNA and protein level were demonstrated in lung tissue, which was accompanied by increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and consumption of glutathione (GSH). N-acetylcysteine (NAC), buthionine sulfoximine (BSO) and GSH-monoethyl ester (GSH-MEE) were injected into mice via caudal vein to regulate glutathione (GSH) level in lung. Alterations of lu...Continue Reading

Citations

May 11, 2019·Cellular and Molecular Life Sciences : CMLS·Sandra Chánez-ParedesMichael Schnoor
Oct 6, 2020·Oxidative Medicine and Cellular Longevity·Zhuanzhuan QiangHong Jiang
Jun 27, 2020·Zeitschrift Für Naturforschung. C, a Journal of Biosciences·Haiying FuMayu Huang
May 25, 2021·Frontiers in Medicine·Mengdi QuChanghong Miao
Jun 24, 2021·Immunopharmacology and Immunotoxicology·Weixin LiRuiyun Li
Jul 27, 2021·BioMed Research International·Qian DouHua Gan
Jul 15, 2021·Cardiovascular Drugs and Therapy·Xiyu ZhangYan Meng
May 19, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Qiuhua ChenFengjie Huang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis