bims-polyam 2023-07-23 papers

Issue of 2023–07–23
four papers selected by
Sebastian J. Hofer, University of Graz

Dev Med Child Neurol. 2023 Jul 19.

André S Bachmann, Elizabeth A VanSickle, Julianne Michael, Marlie Vipond, Caleb P Bupp.

Bachmann-Bupp syndrome (BABS) is a neurodevelopmental disorder characterized by developmental delay, hypotonia, and varying forms of non-congenital alopecia. The condition is caused by 3'-end mutations of the ornithine decarboxylase 1 (ODC1) gene, which produce carboxy (C)-terminally truncated variants of ODC, a pyridoxal 5'-phosphate-dependent enzyme. C-terminal truncation of ODC prevents its ubiquitin-independent proteasomal degradation and leads to cellular accumulation of ODC enzyme that remains catalytically active. ODC is the first rate-limiting enzyme that converts ornithine to putrescine in the polyamine pathway. Polyamines (putrescine, spermidine, spermine) are aliphatic molecules found in all forms of life and are important during embryogenesis, organogenesis, and tumorigenesis. BABS is an ultra-rare condition with few reported cases, but it serves as a convincing example for drug repurposing therapy. α-Difluoromethylornithine (DFMO, also known as eflornithine) is an ODC inhibitor with a strong safety profile in pediatric use for neuroblastoma and other cancers as well as West African sleeping sickness (trypanosomiasis). Patients with BABS have been treated with DFMO and have shown improvement in hair growth, muscle tone, and development.

DOI: https://doi.org/10.1111/dmcn.15687

J Econ Entomol. 2023 Jul 19. pii: toad126. [Epub ahead of print]

Bivoltine cocoon color sex-limited breeds of Bombyx mori (Lepidoptera: Bombycidae) show enhanced economic performance and fecundity following spermidine supplementation.

Madhavi Kasa, Seetharamulu Jolapuram, Anugata Lima, Brinda Goda Lakshmi Didugu, Jagannatha Raju Poosapati, Anitha Mamillapalli.

Sericulture has immense economic significance. Separating male and female silkworm pupae for egg production in grainage is a laborious task; hence, sex-limited breeds for cocoon color are advantageous for this process. The major constraint in sex-limited breeds is their low fecundity. Sex-limited female moths lay a lower number of eggs than nonsex-limited breeds. Polyamine, spermidine was shown to improve fecundity in several organisms, including the silkworm, Bombyx mori L. In the present study, cocoon color sex-limited breeds, HTO2SL, APS27SL, and SLFC27, were selected and fed with spermidine to improve fecundity and nutritional efficiency. The fifth-instar silkworm larvae of the selected breeds were subjected to standard rearing conditions with and without spermidine supplementation up to spinning. The spermidine-supplemented sex-limited breeds exhibited a significant increase in fecundity, nutritional indices, and economic parameters compared with the control sex-limited breeds. Among the 3 sex-limited breeds tested, the performance of APS27SL improved significantly.

Keywords: Bombyx mori ; fecundity nutritional index; sex-limited breed; silkworm; spermidine

DOI: https://doi.org/10.1093/jee/toad126

Cell Rep. 2023 Jul 13. pii: S2211-1247(23)00811-2. [Epub ahead of print]42(7): 112800

The human placenta exhibits a unique transcriptomic void.

Sungsam Gong, Francesca Gaccioli, Irving L M H Aye, Giulia Avellino, Emma Cook, Andrew R J Lawson, Luke M R Harvey, Gordon C S Smith, D Stephen Charnock-Jones.

The human placenta exhibits a unique genomic architecture with an unexpectedly high mutation burden and many uniquely expressed genes. The aim of this study is to identify transcripts that are uniquely absent or depleted in the placenta. Here, we show that 40 of 46 of the other organs have no selectively depleted transcripts and that, of the remaining six, the liver has the largest number, with 26. In contrast, the term placenta has 762 depleted transcripts. Gene Ontology analysis of this depleted set highlighted multiple pathways reflecting known unique elements of placental physiology. For example, transcripts associated with neuronal function are in the depleted set-as expected given the lack of placental innervation. However, this demonstrated overrepresentation of genes involved in mitochondrial function (p = 5.8 × 10-10), including PGC-1α, the master regulator of mitochondrial biogenesis, and genes involved in polyamine metabolism (p = 2.1 × 10-4).

Keywords: CP: Developmental biology; CP: Molecular biology

DOI: https://doi.org/10.1016/j.celrep.2023.112800

Cell Rep. 2023 Jul 14. pii: S2211-1247(23)00809-4. [Epub ahead of print]42(7): 112798

Spermine is a natural suppressor of AR signaling in castration-resistant prostate cancer.

Xiao Li, Fei Li, Fei Ye, Haotian Guo, Wentao Chen, Jia Jin, Yiran Wang, Pengfei Dai, Huili Shi, Hongru Tao, Wenzhen Dang, Yiluan Ding, Mingchen Wang, Hualiang Jiang, Kaixian Chen, Naixia Zhang, Dong Gao, Yuanyuan Zhang, Cheng Luo.

In castration-resistant prostate cancer (CRPC), clinical response to androgen receptor (AR) antagonists is limited mainly due to AR-variants expression and restored AR signaling. The metabolite spermine is most abundant in prostate and it decreases as prostate cancer progresses, but its functions remain poorly understood. Here, we show spermine inhibits full-length androgen receptor (AR-FL) and androgen receptor splice variant 7 (AR-V7) signaling and suppresses CRPC cell proliferation by directly binding and inhibiting protein arginine methyltransferase PRMT1. Spermine reduces H4R3me2a modification at the AR locus and suppresses AR binding as well as H3K27ac modification levels at AR target genes. Spermine supplementation restrains CRPC growth in vivo. PRMT1 inhibition also suppresses AR-FL and AR-V7 signaling and reduces CRPC growth. Collectively, we demonstrate spermine as an anticancer metabolite by inhibiting PRMT1 to transcriptionally inhibit AR-FL and AR-V7 signaling in CRPC, and we indicate spermine and PRMT1 inhibition as powerful strategies overcoming limitations of current AR-based therapies in CRPC.

Keywords: AR-FL; AR-V7; CP: Cancer; CRPC; Metabolite; PRMT1; Spermine

DOI: https://doi.org/10.1016/j.celrep.2023.112798