Expression of class 3 aldehyde dehydrogenase (ALDH-3) has been associated with acquired or inherent resistance to oxazaphosphorine (OAP) antineoplastic alkylating agents (eg. cyclophosphamide). We previously demonstrated that expression of transfected rat ALDH-3 can confer OAP-specific resistance in human MCF-7 cells (Bunting, K. D., Lindahl, R., and Townsend, A. J. (1994) J. Biol. Chem. 269, 23197-23203). However, the aldophosphamide intermediate inactivated by human class 1 ALDH (hALDH-1) has not proven to be a good substrate for the purified hALDH-3. We have examined the ability of transfected human or rat ALDH-3 to confer OAP resistance in V79/SDl cells. Clones expressing elevated human (386-5938 milliunits/mg) or rat (4-597 milliunits/mg, benzaldehyde/NADP+ substrate) ALDH-3 activity were 1.3- to 12-fold resistant to mafosfamide relative to control cells (<1 milliunit/mg). Resistance was correlated with hALDH-3 activity, and was reversed by pretreatment with the ALDH inhibitor diethylaminobenzaldehyde. Transfectants were cross-resistant to 4-hydroperoxycyclophosphamide and 4-hydroperoxyifosfamide but not to phosphoramide mustard, ifosfamide mustard, melphalan, or acrolein. DNA interstrand cross-links were reduced commensurately with the fold resistance to mafosfamide in the highest activity clone. A key finding was the detection of a metabolite, most likely carboxyphosphamide, that is formed only by cytosols from cells expressing either class 3 or class 1 ALDH.
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http://dx.doi.org/10.1074/jbc.271.20.11891 | DOI Listing |
J Mol Endocrinol
January 2025
M Datta, Functional Genomics, CSIR - Institute of Genomics and Integrative Biology, New Delhi, India.
Delayed wound closure is a significant hallmark associated with diabetes. A previous study from our laboratory identified decreased levels of Dicer and miRNAs together with altered levels of wound healing genes in the wounded tissues of diabetic rats. Comprehensive regulators of these wound healing genes mapped onto the PRC2 (polycomb repressive complex 2) complex.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing, 400016, PR China. Electronic address:
Ethnopharmacological Relevance: Stephania rotunda Lour., a medicinal herb, has been utilized in both Traditional Chinese Medicine (TCM) and Traditional Indian Medicine to treat conditions such as fever, dysentery, and inflammation. Cepharanthine (CEP), a primary active ingredient of Stephania rotunda Lour.
View Article and Find Full Text PDFInt J Chron Obstruct Pulmon Dis
January 2025
Department of Respiratory and Critical Care Medicine, Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
Background: Bone marrow mesenchymal stem cell (BMSC) therapy is a novel approach for treating COPD. However, the difficulty in engraftment and easy clearance of BMSCs in vivo has hindered their clinical application. Hence, exploring effective methods to improve the engraftment and differentiation rates of BMSCs in vivo is urgent.
View Article and Find Full Text PDFActa Physiol (Oxf)
February 2025
Department of Physiology, Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan.
Aim: Chronic stress elevates blood pressure, whereas regular exercise exerts antistress and antihypertensive effects. However, the mechanisms of stress-induced hypertension and preventive effects through exercise remain unknown. Thus, we investigated the molecular basis involved in autonomic blood pressure regulation within the amygdala.
View Article and Find Full Text PDFJ Cell Biochem
January 2025
Department of Integrated Traditional Chinese Medicine and Western Medicine, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Gengnianchun (GNC) is a traditional remedy used for diminished ovarian reserve, but its underlying mechanisms remain unclear. This study aimed to explore these mechanisms in human granulosa-like cancer (KGN) cells pretreated with medicated rat serum (MRS) before HO exposure. MRS pretreatment significantly alleviated HO-induced cell damage, including improvements in cell viability, superoxide dismutase and GSH-Px activities, and Bcl-2 expression.
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