128 citations,
December 2006 in “Journal of Biological Chemistry” 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.
91 citations,
July 2004 in “Journal of Biological Chemistry” 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.
54 citations,
February 2002 in “Carcinogenesis” 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.
54 citations,
May 2001 in “Journal of Investigative Dermatology” 71 citations,
May 1996 in “Journal of Investigative Dermatology” The study investigated the role of ornithine decarboxylase (ODC) in hair follicle function using transgenic mice that overexpressed a mutated ODC transgene in hair follicle keratinocytes. These mice experienced normal initial hair growth but lost their hair completely 2-3 weeks after birth, coinciding with the onset of ODC overexpression and the development of follicular cysts. The study found that the ODC inhibitor 2-difluoromethylornithine could prevent hair loss and partially restore normal skin histology if administered early, and it could also reactivate hair growth in mice with complete hair loss. The results suggested that ODC played a crucial regulatory role in mouse hair follicles.
