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Biomedical subjects

L M Fitzgerald

Publications and source records attributed to L M Fitzgerald.

7 recordsLinked to original sources
PubMed1989

Adverse effects of gossypol analogs on TM4 cell mitochondrial function.

Three aqueous-soluble gossypol Schiff's bases, SP562: bis-8,8'-[(N-(2-(dimethylamino)ethyl]-iminomethylene]- 1,1',6,6',7,7'-hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-2,2'-binaphthalene dihydrochloride; SP563: bis-8,8'-[(N-(2-(diethylamino)ethyl]-iminomethylene]-1,1',6,6',7,7'- hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-2,2'-binaphthalene dihydrochloride; and SP564: bis-8,8'-[(N-(2-(diethylamino)propyl]-iminomethylene]-1,1',6,6',7,7'- [hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-2,2'-binaphthalene dihydrochloride, were examined for their effects on TM4 cell mitochondrial function and proliferation. Among the three gossypol analogs, SP562 had the most severe effect on decreasing TM4 cell population that accumulated rhodamine 123 into their mitochondria. This adverse effect exerted by SP562, however, was not as strong as that caused by (+/-) gossypol acetic acid of the same molarity. On the other hand, SP564 had the most severe effect on proliferation of TM4 cells. This severe effect was even more so than that caused by an equimolarity of (+/-) gossypol acetic acid.

Animals↗
PubMed1988

Egg-penetration ability and structural properties of human sperm prepared by Percoll-gradient centrifugation.

Human sperm with a high zona-free hamster egg-penetration ability were obtained by centrifuging freshly ejaculated sperm through a discontinuous two-step (47% and 90%) Percoll gradient at 600g at room temperature for 30 min. Highly motile sperm with good penetration ability were recovered in the pellet fraction (Per-sperm), whereas those with low penetration ability were in the gradient interface. The increased penetration ability of Per-sperm, as compared to sperm capacitated by other methods such as a single-tube swim-up or multiple-tube swim-up preparation, was not due to an increased proportion of acrosome reacted sperm. Rather, transmission electron microscopy indicated that Per-sperm were devoid of coating envelopes, which were present around both the head and tail regions of noncapacitated and single-tube swim-up sperm. Changes to the surface of Per-sperm were demonstrated by their decreased interaction with UEA I lectin, which binds specifically to fucose residues. Removal of the coating envelopes as well as other changes on the sperm surface may lead to an enhanced binding of Per-sperm to the oocyte. In addition, 99% of Per-sperm contained chromatin that was fully condensed. By contrast, about 15% of swim-up sperm still possessed incompletely condensed chromatin. With a higher penetration ability, "clean" appearance, and homogeneity of condensed chromatin, Per-sperm are recommended for insemination and studies of human sperm capacitation.

Centrifugation, Density Gradient↗
PubMedDate not supplied

Differential effects of (+) and (-) gossypol enantiomers on mitochondrial function and proliferation of cultured TM4 cells.

The in vitro effects of (+) and (-)gossypol enantiomers on the mitochondrial functions of mouse transformed Sertoli, TM4 cells were investigated by monitoring mitochondrial rhodamine 123 accumulation. When TM4 cells were cultured in medium without fetal calf serum, 5 micrograms/ml of both enantiomers caused similar declines in mitochondrial rhodamine 123 staining. By contrast, (-)gossypol had a greater adverse action than did (+)gossypol on the mitochondrial of TM4 cells that were cultured in medium supplemented with 2% fetal calf serum. Construction of dose response curves for the effects of the two enantiomers on rhodamine 123 accumulation by TM4 cells after 5 hr of drug treatment gave an EC50 of 7.5 micrograms/ml for the (-)gossypol isomer compared with 18 micrograms/ml for the (+)gossypol isomer. Similarly, TM4 cell proliferation was also more disturbed by (-)gossypol in medium supplemented with other concentrations of fetal calf serum. The results suggest that the lower effect of (+)gossypol on TM4 cells may be attributed to its higher affinity to serum components, which may impede its entrance into TM4 cells.

Animals↗
PubMedDate not supplied

Incorporation of gossypol and formation of its protein conjugates in mouse transformed Sertoli (TM4) cells.

Mitochondria of both mouse transformed Sertoli (TM4) cells and primary-cultured rat and mouse Sertoli cells were shown to be preferentially affected by gossypol (Tanphaichitr et al, 1984). To investigate whether this selective effect was due to a greater of TM4 cells to accumulate gossypol, TM4 and other somatic cell lines, including dog (MDCK) and kangaroo (PtK2) kidney epithelial cells, rat embryo fibroblasts (Rat-1) and mouse BALB/c 3T3 fibroblasts, were incubated with [14C]gossypol and the incorporated specific activity of the drug was assessed. The results indicate that TM4 cells accumulated [14C]gossypol at the highest level. Incorporated [14C]gossypol appeared to bind to TM4 cell macromolecules and remained in the dialysis tubing after extensive dialysis. Characterization of these gossypol-conjugated proteins by SDS-polyacrylamide gel electro-proteins had apparent Mr's of 92,500, 70,000, 63,200, 60,000, 58,100, 54,000, 52,000, 50,000, 47,500, 40,000 37,000, 35,000, 30,000, 20,000, and 14,500 daltons. Conjugation of these proteins with gossypol may result in macromolecular dysfunction and abnormal structure.

Animals↗