bims-polyam 2024-06-23 papers

Issue of 2024–06–23
three papers selected by
Sebastian J. Hofer, University of Graz

Am J Physiol Cell Physiol. 2024 Jun 17.

The role of polyamine metabolism in cellular function and physiology.

Ryan S Schibalski, Anastasia S Shulha, Betty Tsao, Oleg Palygin, Daria V Ilatovskaya.

Polyamines are molecules with multiple amino groups that are essential for cellular function. The major polyamines are putrescine, spermidine, spermine, and cadaverine. Polyamines are important for posttranscriptional regulation, autophagy, programmed cell death, proliferation, redox homeostasis, and ion channel function; their levels are tightly controlled. High levels of polyamines are associated with proliferative pathologies such as cancer, while low polyamine levels are observed in aging, and elevated polyamine turnover enhances oxidative stress. Polyamine metabolism is implicated in a variety of pathophysiological processes in the nervous, immune, and cardiovascular systems. Currently, manipulating polyamine levels is under investigation as a potential preventive treatment in several pathologies, including aging, ischemia/reperfusion injury, pulmonary hypertension, and cancer. Although polyamines have been implicated in a plethora of intracellular mechanisms, our understanding of these processes remains incomplete and is a topic of ongoing investigations. Here, we discuss the regulation and cellular functions of polyamines, their role in physiology and pathology, and emphasize the current gaps in knowledge and potential future research directions.

Keywords: Cellular function; Pathophysiology; Physiology; Polyamines; Sex differences

DOI: https://doi.org/10.1152/ajpcell.00074.2024

Trends Endocrinol Metab. 2024 Jun 18. pii: S1043-2760(24)00126-7. [Epub ahead of print]

Polyamine metabolism in macrophage-adipose tissue function and homeostasis.

Didier F Pisani, Daniele Lettieri-Barbato, Stoyan Ivanov.

Intracellular metabolism is a crucial regulator of macrophage function. Recent evidence revealed that the polyamine pathway and subsequent hypusination of eukaryotic initiation factor 5A (eIF5A) are master regulators of immune cell functions. In brown adipose tissue (BAT), macrophages show an impressive degree of heterogenicity, with specific subsets supporting adaptive thermogenesis during cold exposure. In this review, we discuss the impact of polyamine metabolism on macrophage diversity and function, with a particular focus on their role in adipose tissue homeostasis. Thus, we highlight the exploration of how polyamine metabolism in macrophages contributes to BAT homeostasis as an attractive and exciting new field of research.

Keywords: eIF5A; hypusination; inflammation; monocyte; thermogenesis

DOI: https://doi.org/10.1016/j.tem.2024.05.008

Asian J Pharm Sci. 2024 Jun;19(3): 100924

A PET probe targeting polyamine transport system for precise tumor diagnosis and therapy.

Ming Zhou, Xiaoqin Yin, Bei Chen, Shuo Hu, Wenhu Zhou.

Polyamine metabolism dysregulation is a hallmark of many cancers, offering a promising avenue for early tumor theranostics. This study presents the development of a nuclear probe derived from spermidine (SPM) for dual-purpose tumor PET imaging and internal radiation therapy. The probe, radiolabeled with either [68Ga]Ga for diagnostic applications or [177Lu]Lu for therapeutic use, was synthesized with exceptional purity, stability, and specific activity. Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells, showcasing outstanding tumor localization and target-to-non-target ratio. Mechanistic investigations employing polyamines, non-labeled precursor, and polyamine transport system (PTS) inhibitor, consistently affirmed the probe's targetability through recognition of the PTS. Notably, while previous reports indicated PTS upregulation in various tumor types for targeted therapy, this study observed no positive signals, highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis. Furthermore, when labeled with [177Lu], the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival. Investigations into biodistribution, excretion, and biosafety in healthy humans laid a robust foundation for clinical translation. This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics, offering promising prospects for clinical implementation.

Keywords: Melanoma; PET imaging; Polyamine metabolism; Radiopharmaceutical; Spermine

DOI: https://doi.org/10.1016/j.ajps.2024.100924