Changes in hepatic polyamine catabolism in elderly rats

Abstract: Aims/Background: Given the important role of polyamines (putrescine, spermidine, spermine) in the modulation of macromolecular syntheses, gene expression and proteolysis, alterations in their metabolic pathways could be relevant during senescence. Since the few existing data address mainly polyamine biosynthesis, we studied the oxidative catabolism of polyamines in the liver of rats 3–36 months of age. Methods: Polyamine oxidase activity was fluorimetrically measured using N¹-acetyl-spermine as substrate. Spermidine/spermine N¹-acetyltransferase and diamine oxidase were measured by radiochemical methods using labeled acetyl-coenzyme A and putrescine, respectively, as substrate. Polyamines were separated by HPLC and fluorimetrically quantified after post-column derivatization with o-phthaldialdehyde. Results: Spermidine/spermine N¹-acetyltransferase activity increased in 36-month-old rats and polyamine oxidase activity in 24- and 36-month-old rats. A decline in spermine and increases in spermidine and putrescine in elderly rats suggested an activation of the interconversion pathway of higher into lower polyamines. The activity of diamine oxidase, which degrades putrescine, was enhanced starting from 12 months of age. Conclusion: In the liver of aged rats, an increase in the catabolic enzymes leads to a reconversion of the higher polyamines to putrescine. This increased catabolism may represent an important age-related change and may contribute to impairment of the expression of growth-related genes in senescence.     

Gossypol activates pancreatic polyamine catabolism in normal rats and induces acute pancreatitis in transgenic rats over-expressing spermidine/spermine N1-acetyltransferase

BACKGROUND: The male antifertility agent gossypol has been reported to induce spermidine/spermine N1-acetyltransferase (SSAT) in canine prostate cells. As SSAT is the rate-controlling enzyme in the catabolism of the polyamines and is involved in the development of acute pancreatitis in a recent transgenic rat model, we exposed normal and transgenic rats over-expressing SSAT to gossypol to evaluate its effect on pancreatic polyamine metabolism and organ integrity. METHODS: Pancreatic SSAT activity, polyamine pools, pancreatic histology and plasma 2-amylase activity were determined after different doses of gossypol. RESULTS: Gossypol increased pancreatic putrescine and decreased spermidine and spermine pools in normal rats accompanied by tissue oedema and significantly elevated plasma amylase activity. In transgenic rats, the drug strikingly induced SSAT, profoundly depleted the higher polyamines and caused distinct pancreatitis. The combination of gossypol at doses harmless to transgenic pancreas with an inhibitor of polyamine oxidase caused massive synergistic induction of SSAT, profound depletion of the polyamine pools and acute pancreatitis. CONCLUSIONS: The results indicate that gossypol induces pancreatitis through an activation of polyamine catabolism.     

Age-related changes in polyamine biosynthesis after fasting and refeeding

The effect of aging on ornithine decarboxylase (ODC) activity and polyamine biosynthesis in the proximal small intestine was studied in two groups of male Fisher 344 rats (young [4-month old] and aged [26- to 27-month old]) using a fasting and refeeding model. In control (nonfasted) rats, levels of polyamines (putrescine, spermidine and spermine) and ODC activity were significantly higher in aged compared with young rats. In aged rats, fasting significantly reduced the levels of putrescine by 41%, spermidine by 23%, and spermine by 11%; however, fasting had no effect on polyamine levels in young rats. ODC activity was decreased 75% in young and 50% in aged rats after fasting compared with the respective age-matched controls. Conversely, 2 h after reinstituting a chow diet increased ODC activity by 17-fold in young rats but only 8-fold in aged rats. Putrescine levels were also increased in both age groups after refeeding; however, similar to ODC activity, these increases were much less in aged rats. In addition, spermidine and spermine levels remained significantly depressed in the aged groups even after 24 h of refeeding. These findings suggest that the normal rigid control of gut polyamine biosynthesis and proliferation noted in young rats is markedly altered with aging.     

多胺代谢与大鼠心肌缺血再灌注损伤关系的实验研究

目的 观察缺血再灌注不同时期大鼠心肌多胺代谢变化规律,探讨多胺代谢与心肌缺血再灌注损伤的关系.方法 采用结扎冠状动脉方法复制大鼠在体心肌缺血再灌注损伤模型,应用逆转录聚合酶链反应(RT-PCR)、Western免疫印迹(Western blot)方法分别测定正常、缺血再灌注2 h、6 h、12 h和24 h时心肌鸟氨酸脱羧酶(ODC)和精胺/精脒乙酰转移酶(SSAT)mRNA的转录和蛋白表达水平,并用高效液相色谱仪测定多胺含量变化.结果 心肌缺血再灌注后ODC和SSAT mRNA的转录和蛋白表达均上调,至再灌注24 h时,与假手术组比,ODC mRNA和SSAT mRNA转录分别增加了3.1倍和3.8倍(P＜0.01),ODC和SSAT的蛋白表达分别增加了3.1倍和2.9倍(P＜0.01).精胺、精脒和多胺总代谢池含量减少,至再灌注24 h时,分别比假手术组少了33.6%、35.3%和32.9%,而腐胺多了58.9%(P＜0.01).结论 心肌缺血再灌注损伤可导致多胺代谢失衡,二者密切相关.     

Gossypol Activates Pancreatic Polyamine Catabolism in Normal Rats and Induces Acute Pancreatitis in Transgenic Rats Over-expressing Spermidine/Spermine N 1 -Acetyltransferase

Background: The male antifertility agent gossypol has been reported to induce spermidine/spermine N 1 -acetyltransferase (SSAT) in canine prostate cells. As SSAT is the rate-controlling enzyme in the catabolism of the polyamines and is involved in the development of acute pancreatitis in a recent transgenic rat model, we exposed normal and transgenic rats over-expressing SSAT to gossypol to evaluate its effect on pancreatic polyamine metabolism and organ integrity. Methods: Pancreatic SSAT activity, polyamine pools, pancreatic histology and plasma &#33 -amylase activity were determined after different doses of gossypol. Results: Gossypol increased pancreatic putrescine and decreased spermidine and spermine pools in normal rats accompanied by tissue oedema and significantly elevated plasma amylase activity. In transgenic rats, the drug strikingly induced SSAT, profoundly depleted the higher polyamines and caused distinct pancreatitis. The combination of gossypol at doses harmless to transgenic pancreas with an inhibitor of polyamine oxidase caused massive synergistic induction of SSAT, profound depletion of the polyamine pools and acute pancreatitis. Conclusions: The results indicate that gossypol induces pancreatitis through an activation of polyamine catabolism.     

Increased polyamine levels of normal-appearing mucosa and cancers in DMH induced cancer-bearing colon in rats]

Polyamine levels (putrescine, spermidine, spermine) in normal-appearing colonic mucosa of DMH administrated rats were measured in order to assess their importance as markers of precancerous changes. Mean putrescine, spermidine and spermine levels of normal-appearing mucosa were more than three times mean putrescine, more than twice mean spermidine and more than 1.5 times mean spermine levels of normal colonic mucosa. Mean polyamine levels of colon cancers were higher than those of normal-appearing mucosa but only spermidine level was significantly different between them. The mucosal polyamine levels may be a good biochemical marker to detect precancerous changes. There was no correlation between the polyamine levels and the growth rate of the colon cancers.     

Polyamine metabolism in rat myocardial ischemia-reperfusion injury

This study was focused on investigating the involvement of polyamine metabolism in the myocardial ischemia-reperfusion injury (MIRI) in an in vivo rat model. A branch of the descending left coronary artery was occluded for 30 min followed by 2 h, 6 h, 12 h, and 24 h reperfusion. Then the expression of spermidine/spermine N1-acetyltransferase (SSAT) and ornithine decarboxylase (ODC) and the concentrations of polyamines were assessed. It was found that the expression of SSAT and ODC were upregulated after reperfusion and the concentrations of spermidine and spermine were significantly decreased, while putrescine concentration was significantly increased. The results suggest that MIRI may cause disturbance of polyamine metabolism, and it may play a critical role in MIRI.     

Stimulation of polyamine biosynthesis by follicle-stimulating hormone in serum-free cultures of rat Sertoli cells

Sertoli cells derived from 21-day-old rats were cultured in serum-free Ham's F-10 medium to allow a direct investigation of the effects of FSH on polyamine (PA) biosynthesis in a defined culture system. After 48 h in culture, the basal cellular content consisted predominantly of spermine (1.1 nmol/mg protein) with substantially lower amounts of spermidine (0.1 nmol/mg protein) and undetectable amounts of putrescine. Upon the addition of ovine FSH (3 X 10(-9) M), cellular spermine content became significantly elevated above the control value as early as 1 h after treatment, reaching a 2.5-fold stimulation by 4 h. Spermidine was also elevated by 4 h after FSH treatment, but remained less than 20% of the spermine concentration. At no time did the cellular content of putrescine increase to measurable levels. Extended time-course studies demonstrated that the FSH-induced cellular increase in spermine and spermidine content persisted up to 24 h during the continuous presence of FSH. Bu2cAMP (5 mM) invoked similar changes in PA levels when measured at 4, 8, and 24 h. Ornithine decarboxylase (ODC) activity, which catalyzes the production of putrescine, was increased by FSH in a temporal fashion similar to that of spermine production. Addition of alpha-difluoromethylornithine, an irreversible inhibitor of ODC, blocked increases in both ODC activity and PA in cells stimulated with FSH or Bu2cAMP. Pulse-chase experiments using [3H]ornithine demonstrate that putrescine is initially synthesized, and is subsequently converted to spermidine and spermine. These studies suggest that regulation of PA biosynthesis by FSH is largely expressed as increases in spermine, and to a lesser extent spermidine, suggesting that the more complex PAs may be involved in the regulation of Sertoli cell function.     

Activation of polyamine catabolism in transgenic rats induces acute pancreatitis

Polyamines are required for optimal growth and function of cells. Regulation of their cellular homeostasis is therefore tightly controlled. The key regulatory enzyme for polyamine catabolism is the spermidine/spermine N(1)-acetyltransferase (SSAT). Depletion of cellular polyamines has been associated with inhibition of growth and programmed cell death. To investigate the physiological function SSAT, we generated a transgenic rat line overexpressing the SSAT gene under the control of the inducible mouse metallothionein I promoter. Administration of zinc resulted in a marked induction of pancreatic SSAT, overaccumulation of putrescine, and appearance of N(1)-acetylspermidine with extensive depletion of spermidine and spermine in transgenic animals. The activation of pancreatic polyamine catabolism resulted in acute pancreatitis. In nontransgenic animals, an equal dose of zinc did not affect pancreatic polyamine pools, nor did it induce pancreatitis. Acetylated polyamines, products of the SSAT-catalyzed reaction, are metabolized further by the polyamine oxidase (PAO) generating hydrogen peroxide, which might cause or contribute to the pancreatic inflammatory process. Administration of specific PAO inhibitor, MDL72527 [N(1),N(2)-bis(2,3-butadienyl)-1,4-butanediamine], however, did not affect the histological score of the pancreatitis. Induction of SSAT by the polyamine analogue N(1),N(11)-diethylnorspermine reduced pancreatic polyamines levels only moderately and without signs of organ inflammation. In contrast, the combination of N(1), N(11)-diethylnorspermine with MDL72527 dramatically activated SSAT, causing profound depletion of pancreatic polyamines and acute pancreatitis. These results demonstrate that acute induction of SSAT leads to pancreatic inflammation, suggesting that sufficient pools of higher polyamine levels are essential to maintain pancreatic integrity. This inflammatory process is independent of the production of hydrogen peroxide by PAO.     

Opposite responses of nuclear spermidine N8-acetyltransferase and histone acetyltransferase activities to regenerative stimuli in rat liver.

Experiments performed in different models of hepatic regeneration at the time of maximal DNA synthesis, determined by thymidine kinase activity assay, demonstrated that spermidine N8-acetyltransferase activity increased 48 hr after CCl4 administration (2-fold), 72 hr after CCl4 plus phenobarbital (3-fold) and 24 hr after partial hepatectomy (4.5-fold). On the contrary, at these times histone acetyltransferase activity diminished (approximately twofold) and was unchanged compared with control values in the liver of hepatotoxin-treated and hepatectomized rats, respectively. Histone acetylation was, however, enhanced 1.5-fold before the onset of DNA replication (14 hr), and 3.4-fold after the peak of DNA synthesis (32 hr) in the liver of hepatectomized rats. alpha-Difluoromethylornithine, a specific and irreversible inhibitor of ornithine decarboxylase that was administered to hepatectomized rats, blocked polyamine synthesis, thymidine kinase activity and consequently liver regeneration 24 hr after the surgery. In those conditions, spermidine N8-acetyltransferase activity was decreased approximately twofold, whereas histone acetyltransferase activity was elevated approximately twofold. All these effects were reversed by putrescine coadministration. Altogether, these findings showed that nuclear spermidine N8-acetyltransferase and histone acetyltransferase activities were regulated in opposite ways during the processes associated with liver regeneration. Moreover, they suggested that the polyamines themselves might have a direct or indirect role in this regulation.     

Major pathway for putrescine synthesis induced by 1 alpha,25-dihydroxyvitamin D3 in chick duodenum

We have reported that a single injection of 1 alpha,25-dihydroxyvitamin D3 into vitamin D-deficient chicks produces a marked accumulation of putrescine in the duodenum by an interconversion pathway. In the present study, we examined the effect of N1,N2-bis(2,3-butadienyl)-1,4-butanediamine, a specific irreversible inhibitor of polyamine oxidase, on the duodenal putrescine synthesis induced by 1 alpha,25-dihydroxyvitamin D3. Addition of N1,N2-bis(2,3-butadienyl)-1,4-butanediamine to an assay mixture completely inhibited the activity of duodenal polyamine oxidase in vitro. Prior administration of N1,N2-bis(2,3-butadienyl)-1,4-butanediamine to chicks completely blocked the 1 alpha,25-dihydroxyvitamin D3-induced increase in duodenal accumulation of putrescine in vivo. The increase of the duodenal accumulation of putrescine by 1 alpha,25-dihydroxyvitamin D3 in vitamin D-deficient chicks coincided quantitatively with the amount of N1-acetylspermidine synthesized from spermidine after the injection of the vitamin into the chicks pretreated with the inhibitor of polyamine oxidase. These results clearly indicate that spermidine N1-acetyltransferase plays a preferential role in the increase in duodenal putrescine synthesis by 1 alpha,25-dihydroxyvitamin D3. The rapidly proliferating and maturing epithelium of small intestines will provide a good model for investigating the role of the interconversion of polyamine metabolism in cell growth and differentiation.     

Interleukin-1beta induces elevation of spermidine/spermine N1-acetyltransferase activity and an increase in the amount of putrescine in synovial adherent cells from patients with rheumatoid arthritis

OBJECTIVE: To investigate polyamine metabolism in rheumatoid synovial adherent cells stimulated by interleukin- 1beta (IL-1beta). METHODS: Synovial adherent cells obtained from patients with rheumatoid arthritis (RA) were cultured and incubated in the presence or absence of human recombinant IL-1beta at a concentration of 10 ng/ml for 24 h. The cellular contents of polyamines as well as the activities of spermidine/spermine N1-acetyltransferase (SAT) and ornithine decarboxylase (ODC) were measured. RESULTS: Polyamines in synovial adherent cells decreased significantly after 24 h incubation in the absence of IL-1beta. However, in the presence of IL-Ibeta, putrescine and N'-acetylspermidine increased significantly. No significant difference was observed between the amount of spermidine in synovial adherent cells incubated with and without IL-1beta. Spermine and N8-acetylspermidine in synovial adherent cells incubated with IL-1beta decreased significantly more than in synovial adherent cells incubated without. SAT activity reached a peak 12 h after the addition of IL-1beta and then decreased, while the ODC activity did not increase. SAT activity was elevated by the addition of IL-1beta in a dose dependent manner. CONCLUSION: An increase in the putrescine level in rheumatoid synovial adherent cells as a result of the elevation of SAT activity induced by IL-1beta may play a role in RA.     

Polyamines in 1 alpha, 25-dihydroxycholecalciferol-induced differentiation of human promyelocytic leukemia cells, HL-60

The human promyelocytic leukemia cell line, HL-60, differentiated into macrophage/monocytes in the presence of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3], as assessed by the percentage of morphologically mature cells and their ability to reduce nitroblue tetrazolium. In this study of the mechanism involved, the activities of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase (SAT), the rate-limiting enzymes of polyamine metabolism, as well as the cellular levels of polyamine were measured. ODC activity reached a peak 24 h after the addition of 1 alpha,25(OH)2D3 and then decreased, while SAT activity gradually increased as differentiation commenced. An increase in putrescine and decreases in spermidine and spermine were also observed. Addition of alpha-difluoromethylornithine, an irreversible inhibitor of ODC, with or without methylglyoxalbis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, caused no effect on 1 alpha,25(OH)2D3-induced cell differentiation, although the cellular levels of putrescine and spermidine decreased markedly. Addition of alpha-difluoromethylornithine markedly suppressed cell proliferation; this effect was reversed by the addition of exogenous putrescine. Addition of exogenous spermidine or spermine to overcome activation of SAT also had no effect on 1 alpha,25(OH)2D3-induced cell differentiation. These results suggest both that polyamine metabolism is not important in 1 alpha,25(OH)2D3-induced differentiation of HL-60 cells, but that it is intimately involved in the proliferation of these cells.     

Isoprenaline induced changes in ornithine decarboxylase activity and polyamine content in regions of the rat heart

Isoprenaline stimulated increases in ornithine decarboxylase activity and polyamine content in cardiac tissues are implicated in macromolecular synthesis and cellular growth, but little is known about polyamine metabolism in functionally distinct regions of the heart. We therefore determined regional changes in ornithine decarboxylase activity and polyamine content in the right and left ventricles, septum, and the right and left atria of the rat following the administration of isoprenaline. An increase in ornithine decarboxylase specific activity and tissue polyamine content occurred in all cardiac regions, but the highest ornithine decarboxylase activity was found in the septum. Propranolol inhibited the isoprenaline stimulated ornithine decarboxylase activity in all the regions. Putrescine increased and peaked between 6 and 8 h in right and left ventricles and septum and declined to a control level by 12 h. Following a peak increase at 8 h, spermidine and spermine contents of both ventricles were maintained at peak levels, while those in the septum declined to control values by 12 h. There was no detectable putrescine in the right atria from the control experiments and in either atrium at 2 h following isoprenaline administration. Putrescine content peaked at 6 h in the right atrium and at 8 h in the left atrium and then declined. In both atria there was a peak increase in spermidine and spermine contents between 4 and 8 h. These results show that there is a regional variation in the accumulation of polyamines in the rat heart following isoprenaline administration.     

Polyamine Levels in the Pancreas and the Blood Change according to the Severity of Pancreatitis

Background/Aims: Polyamines are essential to survival, growth, and proliferation of mammalian cells. Previous studies have suggested that the pancreatic polyamine levels may change in acute pancreatitis. In this study, the changes of polyamine levels in the pancreas have been studied with respect to the severity of pancreatitis. We investigated whether there is a relationship in polyamine levels between pancreas and blood, and whether pancreatic and blood polyamine levels change according to the severity of pancreatitis. Methods: In rats, sublethal pancreatitis was induced by intraductal infusion of 2% taurodeoxycholate, while lethal pancreatitis was induced with 6% taurodeoxycholate. Results: Infusion of 6% taurodeoxycholate as compared with 2% resulted in more severe pancreatitis, as revealed by mortality, histology, and serum amylase activity. Pancreatic spermidine/spermine N¹-acetyltransferase was induced early after pancreatitis and was associated with increased putrescine and decreased spermidine levels. The extent of pancreatic necrosis significantly correlated with the polyamine catabolism indicators pancreatic putrescine/spermidine ratio (r = 0.29, p < 0.01) and pancreatic putrescine/spermine ratio (r = 0.32, p < 0.01). The two pancreatic polyamine ratios correlated well also with the red blood cell polyamine ratios (r = 0.75 and r = 0.72, respectively, both p < 0.01). Furthermore, the extent of pancreatic necrosis correlated with red blood cell putrescine/spermidine (r = 0.32, p < 0.01) and putrescine/spermine (r = 0.37, p < 0.01) ratios. Conclusions: Acute experimental pancreatitis is associated with an early pancreatic spermidine/spermine N¹-acetyltransferase induction and consequent changes in polyamine levels in pancreas and red blood cells, depending on the severity of pancreatitis. Because changes in red blood cell spermidine, spermine, and putrescine levels evolve already early during the time course of pancreatitis, and correlate with the extent of pancreatic necrosis, their clinical value as early markers of the severity of acute pancreatitis needs to be further evaluated. Copyright © 2008 S. Karger AG, Basel and IAP     

Aging and intestinal polyamine metabolism in the rat

Hyperproliferation and delayed expression of enzyme activity occur in small intestinal enterocytes of aging rats, and starvation and refeeding result in impaired control of these processes. Since altered polyamine metabolism may accompany changes in enterocyte proliferation, we studied the effects of nutrient manipulation upon cell numbers, ornithine decarboxylase (ODC) activity and polyamine content in jejunum and ileum of 4- to 5- and 26- to 27-month Fischer rats. In both groups, cell numbers fell during starvation and and increased during refeeding. Crypt cell hyperplasia was found in aging animals. Jejunal putrescine, spermine and spermidine content were greater in older rats, fell during starvation, and rose during refeeding. Ileal ODC activity was 66% greater in the aging rats, but jejunal ODC activity was modestly increased in young animals. Intestinal polyamine content correlates with proliferative changes and polyamine metabolism responds appropriately to nutrient manipulation during aging. Dissociation of ODC activity and polyamine content in aging jejunum probably occurred because enterocyte differentiation was delayed. Investigation of intestinal polyamine metabolism may be useful in elucidating deranged proliferative activities found in the intestine of aging rodents.     

Estradiol-17 beta modifies the induction of spermidine/spermine N1-acetyltransferase activity in the liver of lipopolysaccharide-treated mice.

In an attempt to elucidate the effects of estrogen on polyamine metabolism in lipopolysaccharide (LPS)-treated mice, we assayed polyamine content and the activity of spermidine/spermine N1-acetyltransferase (SAT) and ornithine decarboxylase (ODC) in some organs. LPS elevated N1-acetylspermidine levels in the liver and lung and putrescine levels in the liver, lung and spleen. LPS increased the activity of ODC at 6 h and that of SAT at 12 h in the liver. When estradiol-17 beta was simultaneously administered with LPS, the maximum increase in hepatic N1-acetylspermidine levels was found 6 h earlier than in the LPS control. Likewise, the peak of the hepatic SAT activity after LPS-treatment was observed 6 h earlier in the estradiol-17 beta-treated mice than in the LPS control. No such effect of estradiol-17 beta was found in the lung and spleen. The LPS-induced ODC activity was not affected by estradiol-17 beta in the liver, lung or spleen. Estrone and 16 beta-ethylestradiol (an anti-estrogen) were also effective in enhancing the LPS-induced elevation of N1-acetyl-spermidine and putrescine in the liver, while both diethylstilbestrol, which has a potent estrogenic activity without steroid structure and estradiol-17 alpha (a non-estrogenic isomer of estradiol-17 beta) were without effect. Tamoxifen (an estrogen receptor antagonist) did not suppress the estrogen-induced increase in hepatic N1-acetylspermidine levels.     

Human erythrocyte polyamine levels after portal vein embolization

BACKGROUND/AIMS: Polyamine levels in erythrocytes are related to liver regeneration and could be used as an index of liver regeneration after partial hepatectomy. We investigated liver regeneration after portal vein embolization according to the changes of erythrocyte polyamine levels. METHODOLOGY: Levels of polyamines (putrescine, spermidine, and spermine) in erythrocytes were assayed by high-pressure liquid chromatography for 13 patients with hepatocellular carcinoma after portal vein embolization and 16 patients (8 from group reported earlier) after right bisegmentectomy of the liver for hepatocellular carcinoma. In the first group, embolization preceded surgery by 3 weeks. RESULTS: The mean total polyamine level in erythrocytes and the levels of spermidine and spermine were significantly higher at day 7 after embolization, decreasing later. Spermidine and spermine increased by day 7 after partial hepatectomy, decreasing later. Their mean increase was smaller and more gradual when embolization was done before resection than without embolization. CONCLUSIONS: Embolization causes regeneration of the non-embolized portion of the liver, and embolization before liver resection allows regenerative activities of the liver remaining after resection to be lower than without the embolization.     

Modulation of the polyamine biosynthetic pathway in transgenic rice confers tolerance to drought stress

We have generated transgenic rice plants expressing the Datura stramonium adc gene and investigated their response to drought stress. We monitored the steady-state mRNA levels of genes involved in polyamine biosynthesis (Datura adc, rice adc, and rice samdc) and polyamine levels. Wild-type plants responded to the onset of drought stress by increasing endogenous putrescine levels, but this was insufficient to trigger the conversion of putrescine into spermidine and spermine (the agents that are believed to protect plants under stress). In contrast, transgenic plants expressing Datura adc produced much higher levels of putrescine under stress, promoting spermidine and spermine synthesis and ultimately protecting the plants from drought. We demonstrate clearly that the manipulation of polyamine biosynthesis in plants can produce drought-tolerant germplasm, and we propose a model consistent with the role of polyamines in the protection of plants against abiotic stress.     

Hyperoxic lung injury and polyamine biosynthesis. Age-related differences

To determine if lung cell replication and repair might be different between younger (30-day-old) and older (60-day-old) rats, we studied polyamine and DNA biosynthesis in rats exposed to 1.0 atm oxygen for 24, 48, 56, or 72 h. By 24 h, no statistically significant changes were observed, but by 48 h, ornithine decarboxylase and putrescine increased; S-adenosylmethionine decarboxylase activity increased by 56 h in the younger rats but not in the older rats. By 72 h, spermidine, [3H]thymidine incorporation, and the labeling index of cells in the alveolar zone had increased only in the younger rats. During the first 56 h, hyperoxia inhibited DNA synthesis. We conclude that hyperoxia initially suppresses lung cell replication but subsequently, if the rat survives, there are increases in polyamine biosynthesis and cell replication that may be important for the development of oxygen tolerance.