TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity

• Published in: Oxidative medicine and cellular longevity Vol. 2017; no. 2017; pp. 1 - 12
• Main Authors: Liang, Li-Ye, Bai, Yang, Liu, Ming, Gu, Yu-Han, Wang, Yun, Wang, Huai-Liang
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2017; Hindawi; John Wiley & Sons, Inc
• Subjects: Acute coronary syndromes; Animals; Antioxidants; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Chronic illnesses; eIF-2 Kinase - metabolism; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; Genetic aspects; Health aspects; Hemodynamics - drug effects; Hydroquinones - toxicity; Hypertension; Hypotheses; Injuries; Kinases; Laboratory animals; Lung - drug effects; Lung - pathology; Lungs; Male; Methamphetamine; NF-E2-Related Factor 2 - metabolism; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Phosphorylation; Physiology; Proteins; Pulmonary arteries; Quinone; Rats, Wistar; Rodents; Signal Transduction - drug effects; Toxicity; Transcription factors; Vascular Remodeling - drug effects
• ISSN: 1942-0900; 1942-0994; 1942-0994
• DOI: 10.1155/2017/4310475

Methamphetamine (MA) leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS). The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ) alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA), and MA plus TBHQ-treated group (MA + TBHQ). Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity.