Nitrite ion modifies tyrosine and lysine residues of extracellular matrix proteins

Mai T Thao1, Devi Kalyan Karumanchi1, Sally M Yacout1

  • 1Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL, USA.

Insights

Nitrite, a byproduct of inflammation, chemically modifies extracellular matrix proteins in Bruch's membrane. These modifications may initiate the degenerative changes seen in age-related macular degeneration (AMD).

Area of Science:

  • Ophthalmology
  • Biochemistry
  • Pathology

Background:

  • Age-related macular degeneration (AMD) involves degenerative changes in the retinal pigment epithelium and Bruch's membrane.
  • Inflammation is a key risk factor in AMD development and progression.
  • Elevated nitrite levels, a marker of inflammation, are found in AMD tissues.

Purpose of the Study:

  • To investigate the hypothesis that nitrite chemically modifies extracellular matrix (ECM) proteins in Bruch's membrane.
  • To understand the initial chemical alterations in ECM proteins that may lead to AMD pathogenesis.

Main Methods:

  • Used synthetic ECM peptides (fibronectin, laminin) as models for inflammation.
  • Employed liquid chromatography-mass spectrometry (LC/MS) to analyze nitration products.
  • Studied non-enzymatic nitration under controlled conditions.

Main Results:

  • Nitration predominantly occurred on tyrosine residues, forming 3-nitrotyrosine (mass shift of +45 amu).
  • Lysine residues underwent deamination, forming alkene groups (mass loss of -17 amu) or alcohol groups (mass gain of +1 amu).
  • Identified specific chemical modifications resulting from nitrite exposure.

Conclusions:

  • Nitrite-induced chemical modifications of ECM proteins, specifically nitration of tyrosine and deamination of lysine, are demonstrated.
  • These modifications are hypothesized to alter the structure and function of Bruch's membrane, potentially initiating AMD.
  • Provides a molecular mechanism linking inflammation and ECM degradation in AMD.

Related Concept Videos

The Extracellular Matrix01:42

The Extracellular Matrix

Overview
89.2K
The Extracellular Matrix01:29

The Extracellular Matrix

Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
12.3K
Extracellular Matrix01:26

Extracellular Matrix

Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
5.5K
Golgi Matrix Proteins01:12

Golgi Matrix Proteins

Golgi matrix proteins are a group of highly dynamic proteins that maintain the stacked structure of Golgi. These proteins adapt to rapid morphological changes of the Golgi during the cell cycle. During cell division, mild proteolysis removes these connections resulting in Golgi unstacking. In The daughter cells, these proteins help reassemble the unstacked Golgi.
One of the first identified Golgi matrix proteins was GM130, a rod-like protein located in the cis-Golgi. Subsequently, many Golgi...
2.5K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.2K
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
18.8K