Browsing by Subject "iNOS"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Exercise training reverses age-induced inducible nitric oxide synthase upregulation(Texas A&M University, 2005-02-17) Song, WookThe risk of injury, inflammation, and oxidative stress increases in skeletal muscle with aging. It has been postulated that pro-oxidant signaling, including upregulation of inducible nitric oxide synthase (iNOS) contributes to inflammation, pathology, and aging in the brain, liver and heart. Exercise training reduces the risk of injury and inflammation. The purpose of this study was: 1) to identify the mechanisms that upregulate iNOS, pro-oxidant and pro-inflammatory signaling in skeletal muscle, and 2) to identify the mechanisms by which exercise training reduces pro-oxidant signaling. Protein levels and activity of iNOS were measured in 4 groups of male Fischer-344 rats (5 mo and 24 mo, n=10/group), old-control (OC), old-trained (OT), young-control (YC), and young-trained (YT). Exercise training protocol was 60 min at 15 m/min at 15? incline for 5 d/wk for 12 wk. Both iNOS protein expression and activity were significantly higher in OC compared to YC, but exercise training reversed the elevation of iNOS levels lower than OC in tibialis anterior. Surprisingly, NF-κB DNA binding activity was significantly lower in OC than YC, while increased with exercise training in white and red gastrocnemius in both OT and YT. In contrast, protein expression of p65, a regulatory subunit of NF-κB was significantly greater in OC than YC, while exercise training significantly reduced p65 in OT compared to OC from the white gastrocnemius. These data indicate that regulation of NF-κB activity with aging is post-translational and alterations in iNOS expression may result from alternative NF-κB pathways. As decreased NF-κB activity with aging could result in downstream increase in pro-apoptotic signaling, we tested follow-up hypotheses that aging would increase pro-apoptotic regulator Bax and decrease the anti-apoptotic regulator Bcl-2. Bax increased while Bcl-2 decreased in OC in white gastrocnemius when compared to YC. In contrast, exercise training resulted in a dramatic upregulation of Bcl-2 and downregulation of Bax protein expression in OT when compared to OC. These novel results indicate that alterations in pro-inflammatory and pro-apoptotic signaling occur in skeletal muscle during the aging process. Importantly, our findings strongly support the hypothesis that exercise training reverses age-induced changes in pro-inflammatory and pro-apoptotic signaling.Item The relationship between nitric oxide synthase (NOS) and cyclooxygenase (COX) in the control of cervical ripening and parturition(2005-03-14) Stephen Gureasko Marx; Robert E. Garfield, Ph.D., Supervisor; Yurij Vedernikov, M.D., Ph.D.; Thomas Collins, Ph.D.; Randall Given, Ph.D.; Gwendoly V. Childs, Ph.D.; George Saade, M.D.Stephen G. Marx\r\nThe University of Texas Medical Branch at Galveston, April 2005\r\n\r\nSupervisor: Robert E. Garfield\r\n\r\nThe purpose of these studies is to examine if there is relationship between iNOS and COX-2 in the control of cervical ripening and parturition. Cervices were obtained from estrus and timed pregnant Sprague-Dawley rats (n = 4-10 per group) under normal conditions; or after treating with LPS (100ƒÝg i.p.), Onapristone (3mg/rat), progesterone (2.5 mg, twice daily), L-NAME (50mg/day), or SNP (0.3mg/rat). Collagen changes were measured and visualized with the picrosirius polarization method. Expression of iNOS and COX-2 mRNA was determined using RT-PCR. Immunohistochemistry (IHS) was performed for localization of the iNOS and COX-2 enzymes (significance: P<0.05). Picrosirius polarization showed a decrease in the organization and birefringence of the cervical collagen from the non-pregnant state through pregnancy and is supported by changes in the luminosity (P<0.001). The iNOS and COX-2 enzymes were mainly localized in the cervical muscle with labeling also in the vascular smooth muscle and epithelium. Under normal term pregnant conditions, iNOS mRNA levels decrease as COX-2 mRNA levels increased demonstrating an inverse correlation (Spearman r = -0.497; P = 0.00295). Onapristone stimulated preterm labor and/or birth causing a parallel increase in iNOS and COX-2 mRNA demonstrating a positive correlation (Spearman r = 0.456; P = 0.03). Progesterone prolonged pregnancy stimulating a decrease in the iNOS and COX-2 (P=0.036) mRNA. In comparing term to preterm laboring conditions, there is a significant increase in the iNOS mRNA (P=0.004) but not the COX-2 mRNA. LPS enhanced the iNOS mRNA (P<0.001) but had no effect on the COX-2 mRNA. L-NAME had no effect on the COX-2 or iNOS mRNA. SNP decreased the COX-2 and iNOS with the decrease in the iNOS being significant (P=0.007). In conclusion, under normal term pregnant conditions iNOS and COX-2 play an important role in regulating cervical ripening and parturition but the pathways appear to act independently of one another in regulating iNOS and COX-2 expression at the mRNA level. Under preterm laboring conditions, when NO is up regulated and/or over expressed, there may be an interaction between the NO and PG pathways in the control of cervical ripening and parturition. \r\n\r\n