Laura C. Green

Bio: Laura C. Green is an academic researcher from Massachusetts Institute of Technology. The author has contributed to research in topics: Nitrate & Nitroso Compounds. The author has an hindex of 8, co-authored 10 publications receiving 11890 citations.

Nitrate biosynthesis in man.

Abstract: Nitrate metabolism was investigated in long-term metabolic studies in healthy young men. Under conditions of constant low ingestion of nitrate (less than 180 mumol/day per subject), the amount of nitrate excreted in urine was an average of 4-fold greater than the amount ingested. Balance studies with 15NO3- showed that the source of the excess nitrate in urine was the endogenous biosynthesis of nitrate, rather than the emptying of a body pool. Nitrate biosynthesis occurred when nitrate ingestion was high as well as low, and the amounts synthesized appeared to be independent of intake and comparable to the amounts ingested from normal diets. Analysis of the 15NO3- data also revealed that half of ingested nitrate was recovered as urinary nitrate. Because nitrate in urine is the net result of (i) intake, (ii) endogenous synthesis, and (iii) metabolic losses, the magnitude of the losses is such that, despite ongoing synthesis, the amount of nitrate in the urine of people consuming most diets will be less than the amount ingested.

Nitrate synthesis in the germfree and conventional rat

Abstract: Metabolic balance studies show that germfree and conventional Sprague-Dawley rats synthesize nitrate. Equivalent results for germfree and conventional rats eliminate the microflora as obligatory components of nitrate production. Nitrate synthesis appears to be a mammalian process.

In Vivo Dosimetry of 4-Aminobiphenyl in Rats via a Cysteine Adduct in Hemoglobin

Abstract: The feasibility of monitoring doses of 4-aminobiphenyl (ABP) via adduction to hemoglobin was investigated. Rats dosed with ABP (from 0.5 micrograms/kg to 5 mg/kg) formed a stable covalent hemoglobin:ABP adduct. Approximately 5% of a single dose was bound as hemoglobin:ABP; chronic dosing led to an accumulation of the adduct to a level 30 times greater than that found after a single dose. Facile in vitro hydrolysis of the adduct regenerated ABP, allowing detection at the sub-ng level. Human hemoglobin was also readily adducted, using N-hydroxy-ABP in vitro. The predominant site of adduction appeared to be the cysteine residue in hemoglobin. The use of such adducts as dosimeters for arylamine exposures in humans is discussed.

The L-Arginine-Nitric Oxide Pathway

Abstract: The discovery that mammalian cells generate nitric oxide, a gas previously considered to be merely an atmospheric pollutant, is providing important information about many biologic processes. Nitric oxide is synthesized from the amino acid L-arginine by a family of enzymes, the nitric oxide synthases, through a hitherto unrecognized metabolic route -- namely, the L-arginine-nitric oxide pathway1–8. The synthesis of nitric oxide by vascular endothelium is responsible for the vasodilator tone that is essential for the regulation of blood pressure. In the central nervous system nitric oxide is a neurotransmitter that underpins several functions, including the formation of memory. . . .

Nitric Oxide and Peroxynitrite in Health and Disease

Abstract: The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

Nitric oxide as a secretory product of mammalian cells.

Abstract: Evolution has resorted to nitric oxide (NO), a tiny, reactive radical gas, to mediate both servoregulatory and cytotoxic functions. This article reviews how different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule.

Nitric oxide and macrophage function

Abstract: ▪ Abstract At the interface between the innate and adaptive immune systems lies the high-output isoform of nitric oxide synthase (NOS2 or iNOS). This remarkable molecular machine requires at least 17 binding reactions to assemble a functional dimer. Sustained catalysis results from the ability of NOS2 to attach calmodulin without dependence on elevated Ca2+. Expression of NOS2 in macrophages is controlled by cytokines and microbial products, primarily by transcriptional induction. NOS2 has been documented in macrophages from human, horse, cow, goat, sheep, rat, mouse, and chicken. Human NOS2 is most readily observed in monocytes or macrophages from patients with infectious or inflammatory diseases. Sustained production of NO endows macrophages with cytostatic or cytotoxic activity against viruses, bacteria, fungi, protozoa, helminths, and tumor cells. The antimicrobial and cytotoxic actions of NO are enhanced by other macrophage products such as acid, glutathione, cysteine, hydrogen peroxide, or superoxid...