Age and sex modulate renal expression of SGP-2 and transglutaminase and apoptosis of splenocytes, thymocytes, and macrophages.
Age and sex modulate renal expression of SGP-2 and transglutaminase and apoptosis of splenocytes, thymocytes, and macrophages.
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发表时间：
1997-12
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通讯作者：
P. Singhal;K. Reddy;N. Franki;V. Sanwal;A. Kapasi;N. Gibbons;J. Mattana;E. Valderrama
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作者：
P. Singhal;K. Reddy;N. Franki;V. Sanwal;A. Kapasi;N. Gibbons;J. Mattana;E. Valderrama
背景人类的衰老与肾脏质量的进行性损失有关。这被认为是老年人群肾小球滤过率显著降低的原因。此外，衰老与免疫系统受损有关。巨噬细胞、胸腺细胞和脾细胞在维持免疫系统中起重要作用。我们研究了性别和年龄对腹腔巨噬细胞、胸腺细胞和脾细胞凋亡的影响。此外，我们还研究了性别和年龄对肾皮质活性细胞死亡基因mRNA表达的影响。方法4 ~ 12组大鼠分别于2、14、30、50、75、100周龄处死。分离肾皮质、腹膜巨噬细胞、胸腺细胞和脾细胞。分离DNA并在琼脂糖凝胶电泳上运行。TUNEL法和透射电镜观察肾细胞凋亡情况。从肾皮质中分离RNA，用特异性cDNA探针探测与活性细胞死亡相关的基因，如SGP-2、组织蛋白酶-B和组织转氨酶。本实验观察了不同年龄大鼠肾小球系膜细胞凋亡的发生情况。研究雌二醇和睾酮对系膜细胞凋亡的影响。结果2周时，小鼠腹腔巨噬细胞、胸腺细胞和脾细胞均未见DNA断裂。巨噬细胞、脾细胞和胸腺细胞的凋亡随着雄性和雌性动物的年龄增加而增加。与来自年轻大鼠的MC相比，来自老年大鼠的系膜细胞显示出更大的凋亡百分比。雌二醇和睾酮直接影响系膜细胞凋亡。雄性大鼠肾皮质SGP-2和组织转氨酶的mRNA表达随着年龄的增长而增强，而组织蛋白酶-B的表达在雄性和雌性大鼠中均在30周时达到峰值。结论年龄和性别调节肾皮质活性细胞死亡相关基因的mRNA表达。年龄和性别也调节巨噬细胞、脾细胞和胸腺细胞的凋亡。
BACKGROUND Aging in humans has been associated with the progressive loss of renal mass. This has been considered to account for a significant reduction of glomerular filtration rate in the aging population. In addition, aging is associated with a compromised immune system. Macrophages, thymocytes, and splenocytes play an important role in the maintenance of the immune system. We studied the effect of sex and aging on apoptosis of peritoneal macrophages, thymocytes, and splenocytes. In addition, we also studied the effect of sex and aging on mRNA expression of active cell death genes on the renal cortex. METHODS Rats in groups of 4 to 12 were killed at ages 2, 14, 30, 50, 75, and 100 weeks. Renal cortices, peritoneal macrophages, thymocytes, and splenocytes were isolated. DNA was isolated and run on agarose gel electrophoresis. Apoptosis of renal cells was evaluated by the TUNEL method and transmission electron microscopy. RNA was isolated from renal cortices and probed with specific cDNA probes for genes associated with active cell death, such as SGP-2, cathepsin-B, and tissue transglutaminase. Mesangial cells (MC) derived from younger and older rats were examined for the occurrence of apoptosis. The effect of estradiol and testosterone was studied on mesangial cell apoptosis. RESULTS At 2 weeks, peritoneal macrophages, thymocytes, and splenocytes showed no DNA fragmentation. Apoptosis of macrophages, splenocytes, and thymocytes increased with age in the males as well as females. Mesangial cells derived from aged rats showed a greater percentage of apoptosis when compared to MC derived from younger rats. Estradiol and testosterone directly affect mesangial cell apoptosis. Renal cortices of male rats showed enhanced mRNA expression of SGP-2 and tissue transglutaminase with aging; whereas expression of cathepsin-B peaked at 30 weeks in both male and female rats. CONCLUSION Age and sex modulate renal cortical mRNA expression of genes associated with active cell death. Age and sex also modulate apoptosis of macrophages, splenocytes, and thymocytes.