Polyamines in mammalian pathophysiology

Sánchez‐Jiménez, Francisca; Medina, Miguel Ángel; Villalobos-Rueda, Lorena; Urdiales, José Luis

doi:10.1007/s00018-019-03196-0

Cited by 55 publications

(35 citation statements)

References 242 publications

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“…ODC1 promotes tumor growth through the generation of polyamines including putrescine and the higher-order polyamines spermidine and spermine. 29 Our previous study revealed that ODC1 in HCC cells was increased in an acidic microenvironment (simulated Therefore, in the present study, we determined the relationship between lactate metabolism enzyme PKM2 and ODC1 in HCC.…”

Section: Discussionmentioning

confidence: 90%

<p>Simultaneous Inhibition of Ornithine Decarboxylase 1 and Pyruvate Kinase M2 Exerts Synergistic Effects Against Hepatocellular Carcinoma Cells</p>

Zeng¹,

Lan²,

Lei³

et al. 2020

OTT

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Section: Discussionmentioning

confidence: 90%

<p>Simultaneous Inhibition of Ornithine Decarboxylase 1 and Pyruvate Kinase M2 Exerts Synergistic Effects Against Hepatocellular Carcinoma Cells</p>

Zeng¹,

Lan²,

Lei³

et al. 2020

OTT

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“…For instance, spermidine increases autophagy and thus it has important cardioprotective and neuroprotective effects [177]. However, the increased level of polyamines has many pathological effects, e.g., on cancer progression and neurological diseases [178]. For instance, the catabolism of polyamines generates ROS compounds which might have an important role in the generation of immunosuppression but oxidative stress commonly exerts detrimental effects on the host tissues.…”

Section: Arg1 and Arginine Metabolismmentioning

confidence: 99%

Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases

Salminen

2020

J Mol Med

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Chronic low-grade inflammation is a common hallmark of the aging process and many age-related diseases. There is substantial evidence that persistent inflammation is associated with a compensatory anti-inflammatory response which prevents excessive tissue damage. Interestingly, the inflammatory state encountered with aging, called inflammaging, is associated with the anti-inflammaging process. The age-related activation of immunosuppressive network includes an increase in the numbers of myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and macrophages (Mreg/M2c). Immunosuppressive cells secrete several anti-inflammatory cytokines, e.g., TGF-β and IL-10, as well as reactive oxygen and nitrogen species (ROS/RNS). Moreover, immunosuppressive cells suppress the function of effector immune cells by catabolizing l-arginine and tryptophan through the activation of arginase 1 (ARG1) and indoleamine 2,3-dioxygenase (IDO), respectively. Unfortunately, the immunosuppressive armament also induces harmful bystander effects in neighboring cells by impairing host tissue homeostasis. For instance, TGF-β signaling can trigger many age-related degenerative changes, e.g., cellular senescence, fibrosis, osteoporosis, muscle atrophy, and the degeneration of the extracellular matrix. In addition, changes in the levels of ROS, RNS, and the metabolites of the kynurenine pathway can impair tissue homeostasis. This review will examine in detail the harmful effects of the immunosuppressive cells on host tissues. It seems that this age-related immunosuppression prevents inflammatory damage but promotes the tissue degeneration associated with aging and age-related diseases. Key messages • Low-grade inflammation is associated with the aging process and age-related diseases. • Persistent inflammation activates compensatory immunosuppression with aging. • The numbers of immunosuppressive cells increase with aging and age-related diseases. • Immunosuppressive mechanisms evoke harmful bystander effects in host tissues. • Immunosuppression promotes tissue degeneration with aging and age-related diseases.

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“…Metabolism of polyamines (spermine, spermidine, and putrescine) involves combined actions of multiple enzymes [105]. Arginase plays a pivotal role in the polyamine biosynthesis pathway.…”

Section: Polyamine Metabolism In Retinopathymentioning

confidence: 99%

Is the Arginase Pathway a Novel Therapeutic Avenue for Diabetic Retinopathy?

Shosha

Fouda

Narayanan

et al. 2020

JCM

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Diabetic retinopathy (DR) is the leading cause of blindness in working age Americans. Clinicians diagnose DR based on its characteristic vascular pathology, which is evident upon clinical exam. However, extensive research has shown that diabetes causes significant neurovascular dysfunction prior to the development of clinically apparent vascular damage. While laser photocoagulation and/or anti-vascular endothelial growth factor (VEGF) therapies are often effective for limiting the late-stage vascular pathology, we still do not have an effective treatment to limit the neurovascular dysfunction or promote repair during the early stages of DR. This review addresses the role of arginase as a mediator of retinal neurovascular injury and therapeutic target for early stage DR. Arginase is the ureohydrolase enzyme that catalyzes the production of L-ornithine and urea from L-arginine. Arginase upregulation has been associated with inflammation, oxidative stress, and peripheral vascular dysfunction in models of both types of diabetes. The arginase enzyme has been identified as a therapeutic target in cardiovascular disease and central nervous system disease including stroke and ischemic retinopathies. Here, we discuss and review the literature on arginase-induced retinal neurovascular dysfunction in models of DR. We also speculate on the therapeutic potential of arginase in DR and its related underlying mechanisms.

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Polyamines in mammalian pathophysiology

Cited by 55 publications

References 242 publications

<p>Simultaneous Inhibition of Ornithine Decarboxylase 1 and Pyruvate Kinase M2 Exerts Synergistic Effects Against Hepatocellular Carcinoma Cells</p>

<p>Simultaneous Inhibition of Ornithine Decarboxylase 1 and Pyruvate Kinase M2 Exerts Synergistic Effects Against Hepatocellular Carcinoma Cells</p>

Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases

Is the Arginase Pathway a Novel Therapeutic Avenue for Diabetic Retinopathy?

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