Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions

Abstract

The natural polyamines putrescine, cadaverine, spermidine, and spermine are found in all cells. These (poly)cations exert interactions with anions, e.g., DNA and RNA. This feature represents their best-known direct physiological role in cellular functions: cell growth, division, and differentiation. The lung and, more specifically, alveolar epithelial cells appear to be endowed with a much higher polyamine uptake system than any other major organ. In the lung, the active accumulation of natural polyamines in the epithelium has been studied in various mammalian species including rat, hamster, rabbit, and human. The kinetic parameters (Michaelis-Menten constant and maximal uptake) of the uptake system are the same order of magnitude regardless of the polyamine or species studied and the in vitro system used. Also, other pulmonary cells accumulate polyamines but never to the same extent as the epithelium. Although different uptake systems exist for putrescine, spermidine, and spermine in the lung, neither the nature of the carrier protein nor the reason for its existence is known. Some pulmonary toxicological and/or pathological conditions have been related to polyamine metabolism and/or polyamine content in the lung. Polyamines possess an important intrinsic toxicity. From in vitro studies with nonpulmonary cells, it has been shown that spermidine and spermine can be metabolized to hydrogen peroxide, ammonium, and acrolein, which can all cause cellular toxicity. In hyperoxia or after ozone exposure, the increased polyamine synthesis and polyamine content of the rat lung is correlated with survival of the animals. Pulmonary hypertension induced by monocrotaline or hypoxia has also been linked to the increased polyamine metabolism and polyamine content of the lung. In a small number of studies, it has been shown that polyamines can contribute to the suppression of immunologic reactions in the lung.

Spermidine Stimulates T Cell Protein-tyrosine Phosphatase-mediated Protection of Intestinal Epithelial Barrier Function

“…Spermidine is a low molecular weight amine that is water-soluble and fully protonated at physiological pH (23), thereby exhibiting polycationic character. It is the charged chemical nature of spermidine that is thought to play a critical role in the biological activity of the compound, including its activating effect on various enzymes like TCPTP (14,24,25). Although the proposed mechanism by which spermidine increases TCPTP activity has not been clearly defined, it is known that spermidine interacts with TCPTP at the same site as the ␣ 1 -integrin cytoplasmic tail residues 1164 -1179 identified previously to activate TCPTP (6,14).…”

CT imaging as a prognostic indicator for patients with pulmonary injury from acute paraquat poisoning

“…PQ produces toxic peroxide ions that result in cell membrane injury and cell death, finally inducing permanent organ damage or failure if not immediately treated (normally within 4 h) [11]. Serum levels of PQ have been widely used to assess the accumulation of dangerous lung uptake, which normally peaks 4-5 h following exposure, although some studies reported that maximum lung concentration occurs as late as 15 h after exposure [7].…”

Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease

“…Polyamines, which are derived from arginine (ornithine) and decarboxylated S-adenosylmethionine [50], occur in all cells [51] and can reach high micromolar concentrations in brain tissue [52]. Acrolein is formed endogenously from polyamines by copper-dependent amine oxidases (plasma/serum amine oxidase, diamine oxidase, and semicarbazide-sensitive amine oxidase) and by FAD-dependent polyamine oxidases, monoamine oxidase, and spermine/polyamine oxidase [53].…”