Nitration of Tyr37 alters the aggregation pathway of hIAPP and enhances its cytotoxicity.

The amyloid aggregation of hIAPP and the increased level of oxidative stress are closely related to the occurrence and development of type 2 diabetes (T2D). Protein tyrosine nitration is a common post-translational modification under oxidative stress conditions. We previously found that tyrosine nitrated hIAPP (3-NT-hIAPP) has higher cytotoxicity than wild type hIAPP.

Tyrosine nitration of glucagon impairs its function: Extending the role of heme in T2D pathogenesis.

New studies raise the possibility that the higher glucagon (GCG) level present in type 2 diabetes (T2D) is a compensatory mechanism to enhance β-cell function, rather than induce dysregulated glucose homeostasis, due to an important role for GCG that acts directly within the pancreas on insulin secretion by intra-islet GCG signaling. However, in states of poorly controlled T2D, pancreatic α cell mass increases (overproduced GCG) in response to insufficient insulin secretion, indicating decreased local GCG activity. The reason for this decrease is not clear.

Heme and Cu-induced vasoactive intestinal peptide (VIP) tyrosine nitration: A possible molecular mechanism for the attenuated anti-inflammatory effect of VIP in inflammatory diseases.

Vasoactive intestinal peptide (VIP) is a neuropeptide that play an important role in immunoregulation and anti-inflammation. Numerous inflammatory/autoimmune disorders are associated with decreased VIP binding ability to receptors and diminished VIP activation of cAMP generation in immune cells. However, the mechanisms linking oxidative/nitrative stress to VIP immune dysfunction remain unknown.

Mussel inspired multifunctional bovine serum albumin (BSA) coatings loaded with Baicalein (BAI) to enhance osteogenesis and resist oxidative stress for potential application on implant.

Oxidative stress is associated with most traumatic or pathological bone defects, and seriously affects the effect of implantation. The construction of antioxidative and osteogenic coatings is of great significance to accelerate the bone regeneration of implants. In this study, baicalein (BAI), a nature flavonoid drug, was loaded in bovine serum albumin (BSA) by desolvent method to prepare BAI-BSA composite protein, and tannic acid (TA)/BAI-BSA coatings were further built via layer by layer self-assembly technology.

Inhibitory activities of flavonoids from Scutellaria baicalensis Georgi on amyloid aggregation related to type 2 diabetes and the possible structural requirements for polyphenol in inhibiting the nucleation phase of hIAPP aggregation.

Human islet amyloid polypeptide (hIAPP)-mediated cytotoxicity is identified as a potential target for developing new anti-diabetic molecules. Herein, we investigated the effect of the major bioactive compounds of Scutellaria baicalensis Georgi (S. baicalensis), including baicalein, baicalin, wogonin and oroxylin A, on hIAPP aggregation.

Poly(tannic acid) nanocoating based surface modification for construction of multifunctional composite CeONZs to enhance cell proliferation and antioxidative viability of preosteoblasts.

Ceria (CeO) based materials possess many antioxidant enzyme-like activities and unique properties for bone repair, but their free radical scavenging function is still insufficient. In order to deal with the complex oxidative stress environment in bone repair, multifunctional composite CeO nanozymes (CeONZs), featuring multiple antioxidative properties, were constructed surface modification on CeONZs with nanoscale poly(tannic acid) (PTA) coatings. Moreover, we adjusted pH conditions (ranging from 4 to 9) to effectively control the formation and antioxidative properties of PTA coatings on CeONZ surfaces.

Insights Into the Mechanism of Tyrosine Nitration in Preventing β-Amyloid Aggregation in Alzheimer's Disease.

Nitration of tyrosine at the tenth residue (Tyr10) in amyloid-β (Aβ) has been reported to reduce its aggregation and neurotoxicity in our previous studies. However, the exact mechanism remains unclear. Here, we used Aβ peptide with differently modified forms at Tyr10 to investigate the molecular mechanism to fill this gap.

The oxidative reactivity of three manganese(III) porphyrin complexes with hydrogen peroxide and nitrite toward catalytic nitration of protein tyrosine.

Understanding the toxicological properties of MnIII-porphyrins (MnTPPS, MnTMPyP, or MnTBAP) can provide important biochemical rationales in developing them as the therapeutic drugs against protein tyrosine nitration-induced inflammation diseases. Here, we present a comprehensive understanding of the pH-dependent redox behaviors of these MnIII-porphyrins and their structural effects on catalyzing bovine serum albumin (BSA) nitration in the presence of H2O2 and NO2-. It was found that both MnTPPS and MnTBAP stand out in catalyzing BSA nitration at physiologically close condition (pH 8), yet they are less effective at pH 6 and 10.

Near-Infrared Light-Induced Self-Powered Aptasensing Platform for Aflatoxin B1 Based on Upconversion Nanoparticles-Doped BiS Nanorods.

A light source plays a pivotal role in a photofuel cell (PFC)-based self-powered biosensor. Although a visible light source has been extensively employed to drive a PFC, it still has some drawbacks for biosensing due to its relatively high energy. Herein we constructed a PFC-based aptasensor using near-infrared (NIR) light as the irradiation source.

Structure relationship of metalloporphyrins in inhibiting the aggregation of hIAPP.

Metalloporphyrins (FeTBAP, MnTBAP, FeTMPyP and MnTMPyP) have been proposed as effective therapeutic agents in ONOO-related disease including type 2 diabetes (T2D). As these metalloporphyrins share the structural similarities of the planar aromatic conjugation with a valuable class of inhibitors against amyloids fibrillation, they might be effective inhibitors via aromatic π-π stacking interactions with amyloid peptides. Here, we found that the anionic metalloporphyrins (FeTBAP and MnTBAP) are effective inhibitors against hIAPP fibrillation, while, the cationic metalloporphyrins (FeTMPyP and MnTMPyP) only have limited inhibitory effects.

Y12 nitration of human calcitonin (hCT): A promising strategy to produce non-aggregation bioactive hCT.

Irreversible aggregation can extremely limit the bioavailability and therapeutic activity of peptide-based drugs. There is therefore an urgent demand of effective strategy to control peptide aggregation. Recently, we found that tyrosine nitration at certain sites of peptide can effectively inhibit its aggregation.

Peroxynitrite scavenger FeTPPS effectively inhibits hIAPP aggregation and protects against amyloid induced cytotoxicity.

Type 2 diabetes (T2D) is associated with pancreatic β-cell dysfunction, which can be induced by oxidative stress or/and the aggregation of human islet amyloid polypeptide (hIAPP). Therefore, ONOO and hIAPP become the crucial targets of T2D treatment. Previously, we found heme could be an effective inhibitor of hIAPP aggregation.

Dual Anti-/Prooxidant Behaviors of Flavonoids Pertaining to Cu(II)-Catalyzed Tyrosine Nitration of the Insulin Receptor Kinase Domain in an Antidiabetic Study.

Flavonoid, as a potent antioxidant, exerts many beneficial effects in type 2 diabetes, whereas the prooxidative property may be also important in vivo if copper is involved. Here, we chose an insulin receptor kinase domain fragment (KK-1, residues 1126-1165), containing the A-loop of the receptor as well as three key autophosphorylation sites (Tyr, Tyr, and Tyr) associated with receptor signal transduction to investigate the roles and the structure-activity relationship of three antidiabetic flavonoids (kaempferol, luteolin, and apigenin) and two others with a similar structure (diosmetin and genistein), on modulation of Cu(II)-mediated tyrosine nitration and the corresponding effect on its functional phosphorylation in the Cu/HO/NO system. We found that both properties of flavonoid played roles on inhibition of Cu(II)-mediated protein nitration in the HO/NO system: (1) on the one hand, flavonoid scavenged free radicals as antioxidants, inhibited tyrosine nitration, and thus inhibited the reduction of tyrosine phosphorylation caused by tyrosine nitration; and (2) on the other hand, flavonoid promoted OH production as a prooxidant, which increased 3,3'-dityrosine formation.

Hemin-catalyzed biomimetic oxidative phenol-indole [3 + 2] reactions in aqueous media.

A hemin/H2O2 catalytic system for oxidative phenol-indole [3 + 2] coupling in aqueous solution has been developed, enabling benign synthesis of valuable benzofuroindolines under sustainable conditions. Mechanistic studies revealed the dual role of iron porphyrin responsible for both phenol oxidation and Lewis acid activation, which differs from the well-explored chemistry of hemin in carbene and nitrene insertion reactions. A preliminary experiment with cytochrome c showed that the turnover of iron porphyrin was amenable for a macromolecular setting with remarkable efficiency (ca.

Synthesis of a CdS-decorated Eu-MOF nanocomposite for the construction of a self-powered photoelectrochemical aptasensor.

A composite of CdS nanoparticles and a europium metal organic framework (Eu-MOF) (CdS/Eu-MOF) was synthesized. The unique properties of MOFs help to improve the photoelectrochemical (PEC) properties of CdS by reducing charge carrier recombination and utilizing a broader spectrum for light harvesting. Under visible light illumination, the photocurrent of the CdS/Eu-MOF composite modified electrode was about 2.

Structure effect of water-soluble iron porphyrins on catalyzing protein tyrosine nitration in the presence of nitrite and hydrogen peroxide.

Water-soluble iron porphyrins, such as FeTPPS (5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III)), FeTMPyP (5,10,15,20-tetrakis (N-methyl-4'-pyridyl) porphyrinato iron (III) chloride) and FeTBAP (5,10,15,20-tetrakis (4-benzoic acid) porphyrinato iron (III)), are highly active catalysts for peroxynitrite decomposition and thereby have been suggested as therapeutic agent for inflammatory diseases that implicate the involvement of nitrotyrosine formation. Here, we systemically investigated catalytic properties of FeTPPS, FeTMPyP and FeTBAP on protein nitration in the presence of hydrogen peroxide and nitrite. We showed that FeTPPS, FeTBAP and FeTMPyP all exhibited higher peroxidase activity in compared with hemin.

Heme prevents highly amyloidogenic human calcitonin (hCT) aggregation: A potential new strategy for the clinical reuse of hCT.

Irreversible aggregation can extremely limit the bioavailability and therapeutic activity of peptide-based drugs. Thus, peptide fibrillation is an excellent challenge for biotechnological drug development. Human calcitonin (hCT) is such a peptide hormone known for its hypocalcaemic effect but has limited pharmaceutical potential due to a high tendency to aggregate.

Nitration of hIAPP promotes its toxic oligomer formation and exacerbates its toxicity towards INS-1 cells.

Amyloid formation of human islet amyloid polypeptide (hIAPP) is one of the most common pathological features of type 2 diabetes (T2D). Increasing evidences have shown that the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) play an important role in the development of the T2D. Interestingly, our previous studies indicated that heme could bind to hIAPP, and the complex might induce the nitration of tyrosine residue (Y37) of hIAPP in the presence of hydrogen peroxide and nitrite.

Nitration of amyloid-β peptide (1-42) as a protective mechanism for the amyloid-β peptide (1-42) against copper ion toxicity.

It is known that copper ion (Cu(II)) binds to amyloid-β peptide (Aβ), induces Aβ oligomer formation and ultimately exacerbates Aβ-aggregation neurotoxicity in Alzheimer's disease (AD). It becomes interesting to know that how this chemical modification of Aβ would affect interaction of Aβ and Cu(II) and their roles in the development of AD. In this work, we investigated the interaction of Aβ nitration with the toxic Cu(II).

Tyrosine residues of bovine serum albumin play an important role in protecting SH-SY5Y cells against heme/HO/NO-induced damage.

Serum albumin (SA) has been shown to act as a heme scavenger in hemolysis and can protect cell against the toxic effect of heme. However, the mechanism of SA in heme detoxification is not well understood. Interestingly, increasing studies indicate that heme/HO-dependent reaction is unlikely to be the principal cause of heme toxicity in excessive intravascular hemolysis conditions.

Study on the detoxification mechanisms to 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron(III) chloride (FeTPPS), an efficient pro-oxidant of heme water-soluble analogue.

5,10,15,20-Tetrakis (4-sulfonatophenyl) porphyrinato iron(III) chloride (FeTPPS) is a water-soluble analog of heme and widely employed as peroxynitrite scavenger in vivo. However, previous studies have showed that like heme, FeTPPS could also act as an effective pro-oxidant towards appreciable substrates in vitro in the presence of oxidant. The reason that FeTPPS did not show any pro-oxidative damage in previous studies when it was used as peroxynitrite decomposition catalyst in vivo, has not been studied.

Copper Binding Induces Nitration of NPY under Nitrative Stress: Complicating the Role of NPY in Alzheimer's Disease.

Neuropeptide Y (NPY) is a 36 amino acid peptide that regulates a multitude of physiological functions in the central nervous system and has been shown to be involved in Alzheimer's disease (AD). A change in copper homeostasis is a remarkable feature of AD, and the dysregulation may contribute to toxicity in neural cells. Moreover, it has been shown that copper could interact with many neuropeptides and result in catalyzing the production of reactive oxygen species, which may lead to peptide oxidation.

5,10,15,20-Tetrakis(4-sulfonatophenyl)porphyrinato iron(III) chloride (FeTPPS), a peroxynitrite decomposition catalyst, catalyzes protein tyrosine nitration in the presence of hydrogen peroxide and nitrite.

5,10,15,20-Tetrakis(4-sulfonatophenyl)porphyrinato iron(III) chloride (FeTPPS) is a water-soluble heme analog, which has been used as a scavenger of peroxynitrite in many studies. Similar to heme, it may also possess pseudo-peroxidase activity that could cause protein tyrosine nitration through the peroxidase-HO-NO pathway. In this paper, we used western blotting and spectrophotometry analysis to study the capability of FeTPPS in catalyzing protein tyrosine nitration.

Hemin-Graphene Derivatives with Increased Peroxidase Activities Restrain Protein Tyrosine Nitration.

Protein tyrosine nitration is implicated in the occurrence and progression of pathological conditions involving free radical reactions. It is well recognized that hemin can catalyze protein tyrosine nitration in the presence of nitrite and hydrogen peroxide. Generally, the catalytic efficiency is positively correlated to its peroxidase activity.

Strong Inhibitory Effect of Heme on hIAPP Fibrillation.

The deposition of human islet amyloid polypeptide (hIAPP) within β-cells is implicated in the etiology of type 2 diabetes mellitus (T2Dm). It was reported that heme could bind to hIAPP. We speculate that binding may affect the aggregation of hIAPP.