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.

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.271.20.11891DOI Listing

Publication Analysis

Top Keywords

transfected rat
8
human class
8
class aldehyde
8
aldehyde dehydrogenase
8
alkylating agents
8
rat aldh-3
8
aldh-3 confer
8
human
6
protection transfected
4
rat
4

Similar Publications

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 PDF

Cepharanthine relieves nonalcoholic steatohepatitis through inhibiting STAT1/CXCL10 axis-mediated lipogenesis and inflammatory responses.

J 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 PDF

Wnt3a Enhances Mesenchymal Stem Cell Engraftment and Differentiation in a Chronic Obstructive Pulmonary Disease Rat Model.

Int 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 PDF

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 PDF

Gengnianchun Against HO-Induced Oxidative Damage in KGN Cells via miR-548m/FOXO3 Signaling.

J 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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!