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Spermidine/spermine-N(1)-acetyltransferase (SSAT) was identified as a crucial enzyme regulating cellular polyamine content, impacting normal and neoplastic growth, ion channel regulation, and potentially cancer chemotherapy. SSAT activity was highly regulated and could be induced by various stimuli, affecting polyamine homeostasis and linking polyamine metabolism to lipid and carbohydrate metabolism. Increased SSAT activity led to a futile cycle consuming ATP and acetyl-CoA, and was associated with adverse effects such as pancreatic cell death, tissue growth blockage, behavioral changes, and hair loss. SSAT also interacted with proteins like hypoxia-inducible factor-1 alpha and NF-kappaB, though the exact mechanisms were unclear. While SSAT was considered a potential target for diseases beyond cancer, its broad physiological effects necessitated careful targeting to avoid toxicity.

The study explored how altering the expression of spermidine/spermine N1-acetyltransferase (SSAT) affected fat metabolism in mice. Transgenic mice overexpressing SSAT showed increased metabolic activity through the polyamine pathway, resulting in a leaner phenotype with reduced white adipose acetyl- and malonyl-CoA pools and enhanced glucose and palmitate oxidation. In contrast, SSAT knockout mice had decreased metabolic flux, increased body fat, and lower oxidation rates, especially on a high-fat diet. These results indicated that SSAT expression influenced acetyl- and malonyl-CoA levels, affecting fatty acid biosynthesis and oxidation, and thus body fat accumulation. The study underscored the role of SSAT in polyamine metabolism and its impact on fat metabolism via acetyl-CoA modulation.

The study used transgenic mice with targeted expression of spermidine/spermine N1-acetyltransferase (SSAT) in hair follicle keratinocytes to investigate susceptibility to skin cancer. These K6-SSAT transgenic mice, bred onto a tumor-resistant C57BL/6 background, showed a 10-fold increase in epidermal tumors when exposed to a carcinogenesis protocol involving 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. The transgenic mice exhibited elevated SSAT activity and protein levels, along with increased putrescine and N1-acetylspermidine, indicating enhanced polyamine catabolism. The study concluded that this activation of polyamine catabolism might play a crucial role in chemically induced skin cancer, as evidenced by the early onset and progression to carcinomas in the transgenic mice.

The study involved generating a transgenic mouse line overexpressing the SSAT gene under a mouse metallothionein I promoter, leading to significant changes in tissue polyamine pools and delayed permanent hair loss compared to previous models. The liver was notably affected, with altered polyamine levels. Despite high SSAT mRNA levels, enzyme activity was only moderately increased unless induced by ZnSO4 or the polyamine analogue DENSPM, which caused a dramatic increase in enzyme activity and depletion of liver polyamines, resulting in high mortality and liver damage. The findings suggested that SSAT overexpression made the mice highly sensitive to polyamine analogues, indicating a post-transcriptional regulation mechanism.

Overexpression of spermidine/spermine N1-acetyltransferase (SSAT) in transgenic mice led to putrescine accumulation in the skin, resulting in permanent hair loss by 3 weeks of age, with hair follicles replaced by dermal cysts and epidermal utriculi. This condition mirrored hyperproliferative cutaneous disorders like psoriasis, characterized by delayed epidermal differentiation and altered expression of differentiation markers. Immunohistological analysis confirmed disturbed differentiation in SSAT transgenic skin, and similar changes were observed in organotypic cultures of transfected rat epidermal cells. Reducing putrescine levels through biosynthesis inhibition alleviated skin changes and allowed hair regrowth, indicating that keratinocyte differentiation disorders were responsible for the cutaneous changes in SSAT transgenic mice. This highlighted the importance of polyamine metabolism regulation in keratinocyte maturation.

The study involved generating a transgenic mouse line overexpressing the SSAT gene under a mouse metallothionein I promoter, leading to significant changes in tissue polyamine pools and delayed permanent hair loss compared to previous models. The liver was notably affected, with drastic reductions in spermine and increases in putrescine. Despite high levels of SSAT mRNA, enzyme activity was only moderately elevated unless induced by ZnSO4 or the polyamine analogue DENSPM, which caused a massive increase in enzyme activity and depletion of spermidine and spermine pools. This treatment led to high mortality and liver damage, indicating that SSAT overexpression made the mice highly sensitive to polyamine analogues, suggesting a post-transcriptional regulation mechanism.

The study investigated the effects of intradermal spermidine injections on wool follicle growth in Merino lambs. Three groups of eight lambs received different concentrations of spermidine injections on a small skin patch, with saline as a control on the opposite side. Results showed that spermidine increased the concentration in the skin and stimulated cell division in the follicle bulb, with higher doses leading to greater increases. Fibre length growth rate was also higher with spermidine, although fibre diameter did not change significantly. The study concluded that spermidine injections altered skin spermidine homeostasis, stimulated cell proliferation, and increased fibre growth.

The study developed a capillary gas-chromatographic method to quantitatively determine spermidine (SPD) in hair lotions, which was believed to promote hair growth. The method involved using 1,6-diaminohexane as an internal standard, a methyl silicone capillary column, and a flame ionisation detector. Hair lotion samples were treated with an alkaline solution, extracted with diethyl ether containing ethyl chloroformate, and analyzed after reconstitution in ethyl acetate. The method was validated for specificity, linearity, precision, and accuracy, confirming its effectiveness for measuring SPD in hair lotions.

The document evaluated the health claims related to spermidine and its contribution to normal hair growth. The Panel on Dietetic Products, Nutrition and Allergies assessed the scientific evidence provided to substantiate these claims. The conclusion was that a cause-and-effect relationship between the consumption of spermidine and the contribution to normal hair growth was not established due to insufficient evidence. The panel emphasized the need for more robust scientific data to support such health claims.

In this study, researchers created a transgenic mouse line that overexpressed spermidine/spermine N^1-acetyltransferase, leading to significant alterations in tissue polyamine pools. These changes included the presence of N^1-acetylspermidine, an unusual accumulation of putrescine, and reduced levels of spermidine and spermine. The most notable phenotypic effect was permanent hair loss in mice aged 3 to 4 weeks, associated with the formation of follicular cysts in the dermis, likely due to putrescine's interference with hair follicle cell differentiation and proliferation. Additionally, female mice were infertile, linked to ovarian hypofunction and underdeveloped uteri. This research highlighted the potential of using spermidine/spermine N^1-acetyltransferase overexpression to manipulate polyamine levels in transgenic animals for studying developmental and cancer-related outcomes.

The study explored the impact of overexpressing the enzyme spermidine/spermine N1-acetyltransferase (SSAT) in TRAMP mice, a model for prostate cancer. By cross-breeding these mice with SSAT-overexpressing mice, researchers observed a significant reduction in tumor growth, with genitourinary tract weights being 4 to 12 times less than in TRAMP mice alone by 30 to 36 weeks of age. This tumor suppression was attributed to increased polyamine catabolism, which depleted acetyl-CoA and S-adenosylmethionine, despite increased polyamine biosynthesis. Histopathological analysis showed less advanced tumors in TRAMP/SSAT mice, suggesting that SSAT overexpression could be a promising therapeutic strategy for prostate cancer. Additionally, a genitourinary disease index was developed to assess the treatment's impact, particularly in the C57BL/6 mouse background.

The study explored the interaction between the nuclear protein Hairless (HR) and the polyamine putrescine in the epidermis, revealing a negative regulatory loop. Mutations in HR and overexpression of polyamine enzymes like ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SSAT) led to hair loss and skin papules. The research showed that decreased HR levels resulted in increased ODC expression, and this regulation was influenced by the MYC superfamily of proteins. Elevated putrescine levels reduced HR expression, but the effects differed from HR mutations. Microarray analysis indicated that putrescine affected genes related to protein interactions and transcription, suggesting significant implications for epidermal homeostasis and hair follicle cycling.

The study investigated the role of polyamines in hair follicle function and fiber composition in sheep. It found that inhibiting ornithine decarboxylase with alpha difluoromethylornithine altered fiber characteristics but did not inhibit wool follicle growth in culture. Conversely, inhibiting S-adenosylmethionine decarboxylase with methylglyoxal (bis)guanylhydrazone completely inhibited fiber growth, which could be reversed by adding spermidine, but not spermine. The study concluded that polyamines, particularly spermidine, were crucial for hair growth, as evidenced by the ability of spermidine to partially counteract growth depression in methionine-deficient conditions.