bims-polyam 2024-01-14 papers

Issue of 2024–01–14
five papers selected by
Sebastian J. Hofer, University of Graz

Endocrinology. 2024 Jan 09. pii: bqae001. [Epub ahead of print]

Discordant effects of polyamine depletion by DENSpm and DFMO on β cell cytokine stress and diabetes outcomes in mice.

Batoul Hammoud, Jennifer B Nelson, Sarah C May, Sarah A Tersey, Raghavendra G Mirmira.

Type 1 diabetes (T1D) is an autoimmune disease leading to dysfunction and loss of insulin-secreting β cells. In β cells, polyamines have been implicated in causing cellular stress and dysfunction. An inhibitor of polyamine biosynthesis, difluoromethylornithine (DFMO), has been shown to delay T1D in mouse models and preserve β cell function in humans with recent-onset T1D. Another small molecule, N1, N11-diethylnorspermine (DENSpm), both inhibits polyamine biosynthesis and accelerates polyamine metabolism and is currently being tested for efficacy in cancer clinical trials. In this study, we show that DENSpm depletes intracellular polyamines as effectively as DFMO in mouse β cells. RNA sequencing analysis, however, suggests that the cellular responses to DENSpm and DFMO differ, with the two showing effects on cellular proliferation but the latter showing additional effects on mRNA translation and protein folding pathways. In the low-dose streptozotocin-induced mouse model of T1D, DENSpm, unlike DFMO, did not prevent or delay diabetes outcomes but did result in improvements in glucose tolerance and reductions in islet oxidative stress. In non-obese diabetic (NOD) mice, short-term DENSpm administration resulted in a slight reduction in insulitis and proinflammatory Th1 cells in the pancreatic lymph nodes. Longer-term treatment resulted in a dose-dependent increase in mortality. Notwithstanding the efficacy of both DFMO and DENSpm in reducing potentially toxic polyamine levels in β cells, our results highlight the discordant T1D outcomes that result from differing mechanisms of polyamine depletion and, more importantly, that toxic effects of DENSpm may limit its utility in T1D treatment.

Keywords: RNA sequencing; islet; metabolism; polyamines; type 1 diabetes

DOI: https://doi.org/10.1210/endocr/bqae001

J Nutr Biochem. 2024 Jan 05. pii: S0955-2863(24)00003-2. [Epub ahead of print] 109569

Spermidine activates adipose tissue thermogenesis through autophagy and fibroblast growth factor 21.

Yinhua Ni, Liujie Zheng, Liqian Zhang, Jiamin Li, Yuxiang Pan, Haimei Du, Zhaorong Wang, Zhengwei Fu.

Spermidine exerts protective roles in obesity, while the mechanism of spermidine in adipose tissue thermogenesis remains unclear. The present study first investigated the effect of spermidine on cold-stimulation and β3-adrenoceptor agonist-induced thermogenesis in lean and HFD-induced obese mice. Next, the role of spermidine on glucose and lipid metabolism in different types of adipose tissue was determined. Here, we found that spermidine supplementation did not affect cold-stimulated thermogenesis in lean mice, while significantly promoting the activation of adipose tissue thermogenesis under cold stimulation and β3-adrenergic receptor agonist treatment in obese mice. Spermidine treatment markedly enhanced glucose and lipid metabolism in adipose tissues, and these results were associated with the activated autophagy pathway. Moreover, spermidine upregulated fibroblast growth factor 21 (FGF21) signaling and its downstream pathway, including PI3K/AKT and AMPK pathways in vivo and in vitro. Knockdown of Fgf21 or inhibition of PI3K/AKT and AMPK pathways in brown adipocytes abolished the thermogenesis-promoting effect of spermidine, suggesting that the effect of spermidine on adipose tissue thermogenesis might be regulated by FGF21 signaling via the PI3K/AKT and AMPK pathways. The present study provides new insight into the mechanism of spermidine on obesity and its metabolic complications, thereby laying a theoretical basis for the clinical application of spermidine.

Keywords: Autophagy; Brown adipose tissue; FGF21; Obesity; Spermidine; Thermogenesis

DOI: https://doi.org/10.1016/j.jnutbio.2024.109569

J Agric Food Chem. 2024 Jan 12.

Selenium Nanoparticles Mitigate Cadmium Stress in Tomato through Enhanced Accumulation and Transport of Sulfate/Selenite and Polyamines.

Yunyan Kang, Hongyi Qin, Guohu Wang, Bingfu Lei, Xian Yang, Min Zhong.

Accumulation of cadmium (Cd) ions in soil is an increasingly acute ecological problem in agriculture production. Selenium nanoparticles (SeNPs) can mediate Cd tolerance in plants; however, the underlying mechanisms remain unclear. Herein, we show that the foliar application of SeNPs improved the adaptive capacity of tomato plants to decrease Cd-induced damage. SeNPs induced more Cd in roots but not in shoots despite greater accumulation of selenium and sulfur in both tissues and high selenate influx. Additionally, SeNPs significantly increased thiol compounds, including glutathione, cysteine, and phytochelatins, contributing to enhanced Cd detoxification. Importantly, SeNPs induced the expression of sulfate transporters 1:3, S-adenosylmethionine 1 and polyamine transporter 3. Then, experiments with mutants of these genes showed that SeNP-reduced Cd stress largely relies on the levels and shoot-to-root transport of selenium/sulfur and polyamines. These findings highlight the potential of SeNPs to improve crop production and phytoremediation in heavy metal-contaminated soils.

Keywords: cadmium stress; selenium nanoparticles; sulfate/selenate and polyamine

DOI: https://doi.org/10.1021/acs.jafc.3c07504

BMC Plant Biol. 2024 Jan 09. 24(1): 36

Enhancing maize growth through the synergistic impact of potassium enrich biochar and spermidine.

Shoucheng Huang, Ping Huang, Sajid Masood, Muhammad Mazhar Iqbal, Tayyaba Naz, Subhan Danish, Mohammad Javed Ansari, Saleh H Salmen.

Maize cultivated for dry grain covers approximately 197 million hectares globally, securing its position as the second most widely grown crop worldwide after wheat. Although spermidine and biochar individually showed positive impacts on maize production in existing literature, their combined effects on maize growth, physiology, nutrient uptake remain unclear and require further in-depth investigation. That's why a pot experiment was conducted on maize with spermidine and potassium enriched biochar (KBC) as treatments in Multan, Pakistan, during the year 2022. Four levels of spermidine (0, 0.15, 0.30, and 0.45mM) and two levels of potassium KBC (0 and 0.50%) were applied in completely randomized design (CRD). Results showed that 0.45 mM spermidine under 0.50% KBC caused significant enhancement in maize shoot length (11.30%), shoot fresh weight (25.78%), shoot dry weight (17.45%), root length (27.95%), root fresh weight (26.80%), and root dry weight (20.86%) over control. A significant increase in maize chlorophyll a (50.00%), chlorophyll b (40.40%), total chlorophyll (47.00%), photosynthetic rate (34.91%), transpiration rate (6.51%), and stomatal conductance (15.99%) compared to control under 0.50%KBC validate the potential of 0.45 mM spermidine. An increase in N, P, and K concentration in the root and shoot while decrease in electrolyte leakage and antioxidants also confirmed that the 0.45 mM spermidine performed more effectively with 0.50%KBC. In conclusion, 0.45 mM spermidine with 0.50%KBC is recommended for enhancing maize growth.

Keywords: Chlorophyll content; Growth attributes; Nutrients; Potassium-rich biochar; Spermidine

DOI: https://doi.org/10.1186/s12870-024-04722-4

bioRxiv. 2023 Dec 19. pii: 2023.12.19.572290. [Epub ahead of print]

eIF5A controls mitoprotein import by relieving ribosome stalling at the TIM50 translocase mRNA.

Marina Barba-Aliaga, Vanessa Bernal, Cynthia Rong, Brian M Zid, Paula Alepuz.

The efficient import of nuclear-encoded proteins into mitochondria is crucial for proper mitochondrial function. The conserved translation factor eIF5A is primarily known as an elongation factor which binds ribosomes to alleviate ribosome stalling at sequences encoding polyprolines or combinations of proline with glycine and charged amino acids. eIF5A is known to impact the mitochondrial function across a variety of species although the precise molecular mechanism underlying this impact remains unclear. We found that depletion of eIF5A in yeast drives reduced translation and levels of TCA cycle and oxidative phosphorylation proteins. We further found that loss of eIF5A leads to the accumulation of mitoprotein precursors in the cytosol as well as to the induction of a mitochondrial import stress response. Here we identify an essential polyproline-containing protein as a direct eIF5A target for translation: the mitochondrial inner membrane protein Tim50, which is the receptor sub-unit of the TIM23 translocase complex. We show how eIF5A directly controls mitochondrial protein import through the alleviation of ribosome stalling along TIM50 mRNA at the mitochondrial surface. Removal of the polyprolines from Tim50 rescues the mitochondrial import stress response, as well as the translation of oxidative phosphorylation reporter genes in an eIF5A loss of function. Overall, our findings elucidate how eIF5A impacts the mitochondrial function by reducing ribosome stalling and facilitating protein translation, thereby positively impacting the mitochondrial import process.

DOI: https://doi.org/10.1101/2023.12.19.572290