Brain is an endocrine organ through secretion and nuclear transfer of parathymosin

Abstract

This study reports that parathymosin (PTMS) is secreted by hypothalamic stem/progenitor cells (htNSC) to inhibit senescence of recipient cells such as fibroblasts. Upon release, PTMS is rapidly transferred into the nuclei of various cell types, including neuronal GT1-7 cells and different peripheral cells, and it is effectively transferred into neuronal nuclei in various brain regions in vivo. Notably, brain neurons also produce and release PTMS, and because neuronal populations are large, they are important for maintaining PTMS in the cerebrospinal fluid which is further transferable into the blood. Compared with several other brain regions, the hypothalamus is stronger for long-distance PTMS transfer, supporting a key hypothalamic role in this function. In physiology, aging is associated with declines in PTMS production and transfer in the brain, and ptms knockdown in the hypothalamus versus hippocampus were studied showing different contributions to neurobehavioral physiology. In conclusion, the brain is an endocrine organ through secretion and nuclear transfer of PTMS, and the hypothalamus–brain orchestration of this function is protective in physiology and counteractive against aging-related disorders.

Regulation of zinc-dependent enzymes by metal carrier proteins

“…PTMS is found both in the intracellular and extracellular compartments. However, it also contains a nuclear localization signal and has been experimentally identified within the nucleus (Yu et al 2020 ), suggesting that it could potentially regulate other zinc-dependent enzymes there, such as zinc finger proteins.…”

Innate and Adaptive Immunity of Murine Neural Stem Cell-Derived piRNA Exosomes/Microvesicles against Pseudotyped SARS-CoV-2 and HIV-Based Lentivirus

“…Primary NSC models and culture: Primary culture of NSCs was performed as described previously (Li et al, 2012;Yu et al, 2020;Zhang et al, 2017). In brief, the hypothalamus or hippocampus was dissected from newborn C57BL/6 mice, cut into small pieces of approximately 1 mm 3 , and followed by digestion using TrypLE Express enzyme (Life Technologies) for 10 min at 37 °C.…”

Exosomes/microvesicles target SARS-CoV-2 via innate and RNA-induced immunity with PIWI-piRNA system

“…Primary culture of htNSCs was performed as described previously ( 1 , 2 , 3 , 4 ). Hypothalamic tissues from newborn C57BL/6 mice were dissected and cut into pieces around 1 mm 3 size and then digested using TrypLE Express (Gibco) at 37°C for 10 min; cells were centrifuged and resuspended in NSC medium composed of neurobasal-A (Gibco), 0.25% GlutaMAX supplement (Gibco), 2% B27 without vitamin A (Gibco), 10 ng ml −1 EGF (Gibco), 10 ng ml −1 bFGF (Gibco), and 0.5% penicillin–streptomycin (Gibco).…”

“…Lentiviral plasmid vector EF1A promoter–driven hACE2 (VB200000-2751mcf) and mammalian CRISPR lentiviral plasmid vector for PIWIL2 knockout (VB201202-1202gqa) were purchased from Vector Builder. Lentiviruses were produced by co-transfection of cultured HEK293T cells by lentiviral and packaging plasmids, purified via ultracentrifugation and then quantitated with Lenti-X GoStix Plus Kit (TaKaRa), as similarly described in previous publications ( 1 , 2 , 3 , 4 , 40 ).…”

“…Murine neural stem cells (NSCs), in particular hypothalamic NSCs (htNSCs) ( 1 , 2 , 3 , 4 , 5 , 6 ), are known to abundantly release exosomes/microvesicles (Ex/Mv) that are enriched with small RNAs such as miRNAs ( 3 , 4 ). Recently, we revealed that murine NSC Ex/Mv comprise both innate and adaptive immunity effects in breaking pseudotyped SARS-CoV-2 and HIV-based recombinant lentivirus ( 2 ).…”