Postreceptor Mechanisms of Growth Factor Action
Enrique Pimentel in Handbook of Growth Factors, 2017
The two polyamines, putrescine and spermidine, and the diamine, spermine, are ubiquitous in vertebrate cells and are implicated as essential factors in the regulation of cell proliferation and differentiation.28-40 Frequently, the three compounds (spermidine, spermine, and putrescine) are called polyamines (Figure 3.2). In mammalian cells, the polyamines are derived from the amino acids arginine and methionine, and the immediate precursor of the true polyamines is the diamine, putrescine. The polyamines can be interconverted and degraded back to putrescine by the action of specific enzymes. Both acetylated and oxidized forms of polyamines are known to occur naturally, and these polyamine derivatives may be major factors through which the polyamines exert many of their physiological effects.
Hormonal Effects on Gastrointestinal Cancer Growth
Jean Morisset, Travis E. Solomon in Growth of the Gastrointestinal Tract: Gastrointestinal Hormones and Growth Factors, 2017
We have examined the relationship between polyamine levels and GR in samples of colon cancer and mucosa from 40 patients and in mucosa from 11 patients without cancer.97 We found that polyamine levels in colon cancers were significantly higher than in normal colon mucosa from the same patients. Spermidine and spermine were significantly higher in colon mucosa from patients with cancer compared to patients without cancer. Spermidine and the spermidine/ spermine ratio, an index of cell proliferation, were increased in colon cancers with GR compared to cancers without GR. Some patients with colon cancers have elevated fasting gastrin levels.91 Our findings that patients with GR in colon cancers have elevated polyamine levels is evidence that endogenous gastrin may play a trophic role in some human colon cancers.
Immune Control of Pregnancy
Robert E. Garfield, Thomas N. Tabb in Control of Uterine Contractility, 2019
In the same vein, Daya and Clark have reported in the S/N of early human IVF embryos a soluble suppressor activity that would correlate absolutely with successful pregnancy, and as such be predictive of a successful embryo transfer (allowing eventually selection of the good embryos versus the ones doomed to failure).34 The material has been ascribed as a spermine derivative,35 but the very exciting correlation suggested is far from having been reproduced by other laboratories. In fact, as discussed above, there is no need to suppress the action of CTLs or NKs, because embryonic cells are by then intrinsically resistant to cell-mediated lysis,15 and the need for the aforementioned immunosuppressive activities is far from evident.
The pH-triggered polyglutamate brush co-delivery of MDR1 and survivin-targeting siRNAs efficiently overcomes multi-drug resistance of NSCLC
Published in Drug Development and Industrial Pharmacy, 2020
Zhongjuan Wang, Yueqin Liang, Yanqiu Liu, Hongying Xia, Jianqi Liu, Xingfang Jin, Zhongkun Li
The synthesis of DPPGS is illustrated in Scheme 2 and the synthesized polymers were characterized using 1H NMR. Figure 1(A,B) show the spectra of mPEG-b-PBLG and PPGS, respectively. The attribution of peaks was described in our previous study [11]. The spectra of DPPGS was in accordance with the expected structures (Figure 1(C)). The typical peaks of methylene (–CH2CH2O–) of mPEG-NH2 appeared at a (δ = 3.67 ppm). The peaks of methylene connected with amide group appeared at b (δ = 4.27 ppm). The signals at c + d (δ = 1.77–1.90 ppm) were ascribed to the ethylene group (–CH2–CH2–) of BLG units. The signal at k (δ = 7.87 ppm) corresponded to the amide group (–CONH–) of PG. The peaks of j (δ = 1.60–1.80 ppm, –CH2CH2–) and g + i (δ = 2.02–3.60 ppm, –CH2NH–) were attributed to spermine. Compared with the spectrum of mPEG-b-PBLG, the disappearance of the peak of e (δ = 4.82 ppm) demonstrated that the benzyl (–CH2Ph) in the side chain was completely removed. Meanwhile, the appearance of p (δ = 1.75 ppm, –C(CH3)=C(CH3)–) attributed to DMA demonstrated the successful synthesis of DPPGS [14]. The polymerization degree and spermine grafting ratio of DPPGS was 102 and 81.7%, respectively, according to our previous study [11]. However, the grafting ratio of DMA could not be calculated in this study since the characteristic peaks of DMA partly overlap with the peaks of spermine.
Role of the mitochondrial calcium uniporter in Mg2+-free-induced epileptic hippocampal neuronal apoptosis
Published in International Journal of Neuroscience, 2020
Yingjiao Li, Cui Wang, Yajun Lian, Haifeng Zhang, Xianghe Meng, Mengyan Yu, Yujuan Li, Nanchang Xie
Mitochondrial Ca2+ homeostasis is critical for cell survival. Mitochondrial Ca2+ overload can induce cell apoptosis by increasing ROS production, promoting opening of the mPTP, and inducing the release of cytochrome c [18]. In this study, we found that inhibition of the MCU can protect neurons from apoptosis and attenuate neuronal damage induced by AE. We also found that the MCU inhibitor Ru360 reversed the seizure-induced mitochondrial Ca2+ concentration increase and production of mitochondrial ROS, while the mMP level decreased. However, the MCU activator spermine exerted the opposing effects. In addition, Ru360 and spermine did not have a detectable impact on the concentration of mitochondrial Ca2+ [19, 20]. We hypothesized that Ru360 and spermine exerted effects on the basis of the MCU activation induced by seizures. These results support extant findings of previous studies indicating that spermine could exacerbate oxidative stress induced by ischemia–reperfusion [21]. However, a recent study reported that Pb2+-induced ROS production was potentiated by Ru360 or MCU knockdown and reversed by spermine or MCU overexpression [5]. Although the effect of MCU on oxidative stress requires further study, the studies described herein suggest that MCU plays a crucial role in the oxidative stress response.
Nutritional intervention in chronic pain: an innovative way of targeting central nervous system sensitization?
Published in Expert Opinion on Therapeutic Targets, 2020
Jo Nijs, Sevilay Tumkaya Yilmaz, Ömer Elma, Joe Tatta, Patrick Mullie, Luc Vanderweeën, Peter Clarys, Tom Deliens, Iris Coppieters, Nathalie Weltens, Lukas Van Oudenhove, Eva Huysmans, Anneleen Malfliet
Polyamines represent another potential therapeutic target in the area of nutritional interventions for the prevention of post-surgical pain. Polyamines are cationic organic molecules present in all living organisms, with spermidine, spermine, and their precursor putrescine as the main polyamines in mammalian cells [71]. Human gut bacteria synthesize and transport polyamines [71], and polyamine levels increase with inflammation [72]. Polyamines are thought to be involved in the regulation of numerous metabolic and electrophysiological processes in the nervous system, including scavenging of reactive oxygen species, and alteration of polyamine metabolism has been identified in neurodegenerative disease and several types of cancer, resulting in the increased interest of exogenous administration of natural polyamines as innovative treatment [71]. Animal studies support the idea that a polyamine-deficient dietary pattern has analgesic effects on inflammatory pain [73] and reduces pain hypersensitivity [74]. Excitation of N-methyl-D-aspartate (NMDA) receptors is an essential component of the central nervous system sensitization, with polyamines holding the capacity to modulate them [72]. Polyamine-deficient dietary pattern is thought to inhibit tyrosine phosphorylation of the NMDA receptors [72], thereby potentially decreasing the sensitivity of the (central) nervous system.