Sex and age alter plasma membranes of cultured fibroblasts

Abstract

Human skin fibroblasts were taken from age-matched male and female subjects. The cells were then cultured under identical conditions and passage-number matched. Plasma membranes were isolated and membrane enzyme activities, lipid composition, and structure of isolated plasma membranes were measured in order to determine the presence of significant sex differences in human fibroblast membrane properties. The results indicated that plasma membranes from normal female subjects had a 1.6-fold and 3.6-fold higher cholesterol/phospholipid ratio and oleic acid (18:2) content than normal male subjects. The limiting anisotropy and the rotational relaxation time of fluorescence probe molecules such as trans-parinaric acid and 1,6-diphenyl-l,3,5-hexatriene in the plasma membranes was not significantly different from fibroblasts of male versus female normal subjects. The total activity of plasma membrane (Na', K+)-ATPase was significantly higher in female than male normal subjects. A potential 'membrane structural disorder', Huntington's disease, was confirmed in fibroblast membranes from male but not from female Huntington's disease subjects. The possibility that Huntington's disease was a 'premature membrane aging' phenomenon was considered. A comparison of plasma membrane enzymes, lipids, and structure from old and young Huntington's disease subjects did not show differences consistent with accelerated membrane aging as explaining the molecular basis for the disease. The age-dependent differences noted in aged Huntington's disease subjects: increased phosphatidylcholineiphosphatidylethanolamine ratio and sphingomyelin + lysophosphatidylcholine content of fibroblast plasma membranes were not significantly altered when compared to normal age-matched controls. However, (Na +, K+)-ATPase activity was significantly enhanced in fibroblast plasma membranes of older Huntington's disease subjects unlike those of control subjects. In conclusion, sex and age differences in membrane properties of cultured cells represent important potential variables in the elucidation of human genetic disorders that may be membrane-related.The effect of hormonal status in vitro or in vivo on structure and function of membranes is an area where our present knowledge is extremely limited not only for normal subjects but also for those affected by genetic disorders. Direct effects of prostaglandin E on erythrocyte fluidity [I] and of insulin, glucagon, and thyroid hormone on liver plasma membranes [2,3] have been demonstrated. In addition, thyroid status (hyperthyroid vs hypothyroid or euthyroid) dramatically altered the lipid composition and structure of both the verylow-density lipoproteins secreted by the perfused rat liver [4,5] and the isolated liver plasma membranes [3]. Such indirect structural alterations in membranes may be mediated by Ca2+ [3,6 -81 or via altered fatty acid composition of membrane phosphoglycerides [9 -121 and can bc accounted for, at least in part, by altered fatty acid desaturase: enzymes [I21 or altered secretion of v...

Age-Related Permeability Changes in Rabbit Corneas

“…The aging processes in the cornea remain unknown. Aging is associated with a variety of cell changes (10). In general, both the function and composition ofthe cell surface membrane are altered with age.…”