bims-polyam 2022-10-23 papers

Issue of 2022–10–23
four papers selected by
Sebastian J. Hofer, University of Graz

J Exp Bot. 2022 Oct 20. pii: erac411. [Epub ahead of print]

Spermine inhibits PAMP-induced ROS and Ca 2+ burst and reshapes the transcriptional landscape of PTI in Arabidopsis.

Chi Zhang, Kostadin E Atanasov, Rubén Alcázar.

Polyamines are small polycationic amines whose levels increase during defense. Previous studies support the contribution of the polyamine spermine (Spm) to defense responses. However, the potential contribution of Spm to pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) was not completely established. In this work, we compared the contribution of Spm and putrescine (Put) to early and late PTI responses in Arabidopsis. We find that Put and Spm have opposite effects on PAMP-elicited reactive oxygen species (ROS) production, with Put increasing whereas Spm lowering the flg22-stimulated ROS burst. Through genetic and pharmacological approaches, we find that the inhibitory effect of Spm on flg22-elicited ROS production is independent of polyamine oxidation, nitric oxide (NO) and salicylic acid (SA) signaling but resembles chemical inhibition of RBOHD (RESPIRATORY BURST OXIDASE HOMOLOG D). Spm can also suppress ROS elicited by FLS2-independent but RBOHD-dependent pathways, thus pointing to compromised RBOHD activity. Consistent with this, we find that Spm but not Put dampens flg22-stimulated cytosolic Ca 2+ influx. We finally find that both polyamines differentially reshape transcriptional responses during PTI and disease resistance to Pseudomonas syringae. Overall, we provide evidence for the differential contribution of Put and Spm to PTI with an impact on plant defense.

Keywords: NADPH oxidase; Putrescine; ROS; Spermine; defense; pathogen-associated molecular pattern (PAMP); polyamines

DOI: https://doi.org/10.1093/jxb/erac411

Plant Physiol Biochem. 2022 Oct 03. pii: S0981-9428(22)00439-9. [Epub ahead of print]192 172-185

Over-expression of spermidine synthase 2 (SlSPDS2) in tomato plants improves saline-alkali stress tolerance by increasing endogenous polyamines content to regulate antioxidant enzyme system and ionic homeostasis.

Pengju Wang, Zijian Xu, Yong Zhang, Yongbo Ma, Jianyu Yang, Fan Zhou, Yi Gao, Guobin Li, Xiaohui Hu.

Endogenous spermidine can improve the resistance of plants to saline-alkali stress. SlSPDS1 and SlSPDS2 are the main spermidine synthase (SPDS) genes in tomatoes. In comparison with SlSPDS1, SlSPDS2 plays an important role in wild-type tomato seedling under saline-alkali stress. However, limited research has focused on the role of SlSPDS2 in saline-alkali stress. Wild-type (WT) and SPDS gene (SlSPDS2) transgenic over-expression tomato seedlings were used to explore the function of endogenous spermidine on the saline-alkali resistance of tomato seedlings. The results show that SlSPDS2 overexpression under normal conditions and saline-alkali stress increased the content of endogenous free polyamines and the expression levels of polyamine synthesis-related genes in tomato seedlings. Under saline-alkali stress, SlSPDS2 overexpression significantly reduced Na+/K+ ratio, relative electrical conductivity, O2·-, H2O2, and malondialdehyde content, increased Seedling index, relative water content, antioxidant enzyme activities (peroxidase, superoxide dismutase, and catalase), and the contents of proline and soluble sugar in tomato leaf, and mitigated the adverse effect of saline-alkali stress on tomato seedlings. In summary, the overexpression of SlSPDS2 tomato seedlings regulated the ionic homeostasis, antioxidant enzyme system, and osmotic regulatory substances of tomato seedlings living in saline-alkali environment by increasing endogenous free polyamine content, thereby improving the resistance of tomato seedlings against saline-alkali stress.

Keywords: Antioxidant enzymes; Ion homeostasis; Polyamines; Saline-alkali stress; SlSPDS2; Solanum lycopersicum

DOI: https://doi.org/10.1016/j.plaphy.2022.09.025

Front Public Health. 2022 ;10 949170

The association of dietary spermidine with all-cause mortality and CVD mortality: The U.S. National Health and Nutrition Examination Survey, 2003 to 2014.

Huanyu Wu, Jianing Wang, Hongyan Jiang, Xin Liu, Xinyi Sun, Yunyan Chen, Cong Hu, Zheng Wang, Tianshu Han, Changhao Sun, Wei Wei, Wenbo Jiang.

Background: Current studies on the protective effects of dietary spermidine (SPD) on cardiovascular disease (CVD) are mainly limited to animal studies, and the relationship between dietary SPD and CVD mortality remains inconclusive.
Objective: This study aims to evaluate the association between dietary SPD intake and CVD and all-cause mortality.
Methods: A total of 23,894 people enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2014 were recruited for this study. The dietary intake of SPD from 11 specific food origins and total SPD was categorized into tertiles or quartiles. Cox proportional hazard regression models were developed to evaluate the association of SPD intake with CVD and all-cause mortalities.
Results: Among the 23,894 participants, 2,365 deaths, including 736 deaths due to CVD, were documented. After adjustment for potential confounders, compared with participants in the lowest quartile, participants in the highest quartile of total SPD had a significantly lower risk of CVD mortality (HR = 0.68, 95% CI: 0.51-0.91) and all-cause mortality (HR = 0.70, 95% CI: 0.60-0.82); participants in the highest tertiles or quartiles of vegetable-derived SPD, cereal-derived SPD, legume-derived SPD, nut-derived SPD, and cheese-derived SPD had a lower risk of CVD mortality (HR vegetable - derivedSPD = 0.68, 95% CI: 0.54-0.86; HR cereal - derivedSPD = 0.75, 95% CI: 0.57-0.97; HR legume - derivedSPD = 0.68, 95% CI: 0.52-0.88; HR nut - derivedSPD = 0.66, 95% CI: 0.53-0.80; HR cheese - derivedSPD = 0.68, 95% CI: 0.52-0.88) and all-cause mortality (HR vegetable - derivedSPD = 0.73, 95% CI: 0.64-0.84; HR cereal - derivedSPD = 0.80, 95% CI: 0.69-0.93; HR legume - derivedSPD = 0.70, 95% CI: 0.60-0.80;HR nut - derivedSPD = 0.72, 95% CI: 0.64-0.81; HR cheese - derivedSPD = 0.70, 95% CI: 0.61-0.81) than those in the lowest tertiles or quartiles. Moreover, subgroup analysis showed consistent associations among the people with hypertension and hyperlipidemia.
Conclusion: Higher intake of dietary SPD is associated with decreased risk of CVD and all-cause mortality, and among specific food origin SPD, SPD derived from vegetables, cereals, legumes, nuts, and cheese was associated with reduced CVD and all-cause mortality.

Keywords: CVD mortality; NHANES; SPD; all-cause mortality; autophagy

DOI: https://doi.org/10.3389/fpubh.2022.949170

Onco Targets Ther. 2022 ;15 1229-1243

Spermidine Promotes Nb CAR-T Mediated Cytotoxicity to Lymphoma Cells Through Elevating Proliferation and Memory.

Hongxia Wang, Dan Jiang, Liyuan Liu, Yanting Zhang, Miao Qin, Yuliang Qu, Liyan Wang, Shan Wu, Haijin Zhou, Tao Xu, Guangxian Xu.

Purpose: Due to the natural advantages of spermidine in immunity, we investigated the effects of spermidine pretreatment on nanobody-based CAR-T cells (Nb CAR-T) mediated cytotoxicity and potential mechanism.
Patients and Methods: The optimal concentration of spermidine was determined by detecting its impact on viability and proliferation of T cells. The phenotypic characteristic of CAR-T cells, which were treated with spermidine for 4 days, was examined by flow cytometry. The expansion ability of CAR-T cells was monitored in being cocultured with tumor cells. Additionally, CAR-T cells were stimulated by lymphoma cells to test its cytotoxicity in vitro, and the supernatant in co-culture models were collected to test the cytokine production. Furthermore, xenograft models were constructed to detect the anti-tumor activity of CAR-T cells in vivo.
Results: The optimal concentration of spermidine acting on T cells was 5μM. The antigen-dependent proliferation of spermidine pretreatment CD19 CAR-T cells or Nb CAR-T cells was increased compared to control. Central memory T cells(TCM) dominated the CAR-T cell population in the presence of spermidine. When spermidine pretreatment CAR-T cells were stimulated with Daudi cells, the secretion of IL-2 and IFN-γ has been significantly enhanced. The ability of CAR-T cells to lysis Daudi cells was enhanced with the help of spermidine, even at higher tumor loads. Pre-treated Nb CAR-T cells with spermidine were able to control tumor cells in vivo, and therefore prolong mice survival.
Conclusion: Our results revealed that spermidine could promote Nb CAR-T mediated cytotoxicity to lymphomas cells through enhancing memory and proliferation, and provided a meaningful approach to strengthen the anti-tumor effect of CAR-T cells.

Keywords: CAR-T; exhaustion; nanobody; spermidine

DOI: https://doi.org/10.2147/OTT.S382540