Fundamental Mechanisms of the Cell Death Caused by Nitrosative Stress

Fulin Wang; Qiuhuan Yuan; Fengying Chen; Jiaojiao Pang; Chang Pan; Feng Xu; Yuguo Chen

doi:10.3389/fcell.2021.742483

Fundamental Mechanisms of the Cell Death Caused by Nitrosative Stress

Front Cell Dev Biol. 2021 Sep 20:9:742483. doi: 10.3389/fcell.2021.742483. eCollection 2021.

Authors

Fulin Wang^{1

2

3

4

5}, Qiuhuan Yuan^{1

2

3

4

5}, Fengying Chen⁶, Jiaojiao Pang^{1

2

3

4

5}, Chang Pan^{1

2

3

4

5}, Feng Xu^{1

2

3

4

5}, Yuguo Chen^{1

2

3

4

5}

Affiliations

¹ Department of Emergency Medicine, Qilu Hospital, Shandong University, Jinan, China.
² Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
³ Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China.
⁴ Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, China.
⁵ The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Jinan, China.
⁶ Emergency Department, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.

Abstract

Nitrosative stress, as an important oxygen metabolism disorder, has been shown to be closely associated with cardiovascular diseases, such as myocardial ischemia/reperfusion injury, aortic aneurysm, heart failure, hypertension, and atherosclerosis. Nitrosative stress refers to the joint biochemical reactions of nitric oxide (NO) and superoxide (O₂ ^-) when an oxygen metabolism disorder occurs in the body. The peroxynitrite anion (ONOO^-) produced during this process can nitrate several biomolecules, such as proteins, lipids, and DNA, to generate 3-nitrotyrosine (3-NT), which further induces cell death. Among these, protein tyrosine nitration and polyunsaturated fatty acid nitration are the most studied types to date. Accordingly, an in-depth study of the relationship between nitrosative stress and cell death has important practical significance for revealing the pathogenesis and strategies for prevention and treatment of various diseases, particularly cardiovascular diseases. Here, we review the latest research progress on the mechanisms of nitrosative stress-mediated cell death, primarily involving several regulated cell death processes, including apoptosis, autophagy, ferroptosis, pyroptosis, NETosis, and parthanatos, highlighting nitrosative stress as a unique mechanism in cardiovascular diseases.

Keywords: cardiovascular diseases; cell death; nitric oxide; nitrosative stress; peroxynitrite; reactive nitrogen species.

Publication types

Review