The exercising respiratory system

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

E (2008) Ventilatory capacity and its utilisation during exercise. Lung 186

Abstract Inadequate ventilation is not usually considered an exercise-limiting factor because it is thought that the respiratory system's maximum ventilatory capacity is never reached during exercise. This so-called reserve can be defined as the difference between the ventilated volume, attained during a maximum voluntary ventilation manoeuvre (MVV) and the maximum ventilation ð _ V E max Þ achieved during exercise. This study explores the relationship between ventilatory capacity, the MVV manoeuvre, and respiratory function. Twelve healthy adults completed a maximal cycle test and 12-, 30-, and 60-s MVV manoeuvres while seated or standing. The MVV 12 manoeuvre produced the largest ventilation volume (115 ± 22 vs. ð _ V E max Þ 102 ± 23 L min -1 ), signifying a reserve of 13%. With longer MVV (30 and 60 s) manoeuvres, the ventilated volume and ð _ V E max Þ were the same, signifying no reserve. MVV increased with the forced expiratory volume at one second, FEV 1 . The breath rates were approximately 120 vs. 48 ± 6 breaths min -1 and tidal volumes were approximately 1 vs. 2.2 ± 0.5 L during the MVV and exercise, respectively. The longer MVV manoeuvre provides the best estimate of ventilatory capacity and shows that 100% of the reserve is used during maximal exercise. A nomogram relating MVV to FEV 1 is shown

Sp1 and Sp3 mediate constitutive transcription of the human hyaluronan synthase 2 gene

The linear glycosaminoglycan hyaluronan (HA) is synthesized at the plasma membrane by the HA synthase (HAS) enzymes HAS1, -2, and -3 and performs multiple functions as part of the vertebrate extracellular matrix. Up-regulation of HA synthesis in the renal corticointerstitium, and the resultant extracellular matrix expansion, is a common feature of renal fibrosis. However, the regulation of expression of these HAS isoforms at transcriptional and translational levels is poorly understood. We have recently described the genomic structures of the human HAS genes, thereby identifying putative promoter regions for each isoform. Further analysis of the HAS2 gene identified the transcription initiation site and showed that region F3, comprising the proximal 121 bp of promoter sequence, mediated full constitutive transcription. In the present study, we have analyzed this region in the human renal proximal tubular epithelial cell line HK-2. Electrophoretic mobility shift and promoter assay data demonstrated that transcription factors Sp1 and Sp3 bound to three sites immediately upstream of the HAS2 transcription initiation site and that mutation of the consensus recognition sequences within these sites ablated their transcriptional response. Furthermore, subsequent knockdown of Sp1 or Sp3 using small interfering RNAs decreased constitutive HAS2 mRNA synthesis. In contrast, significant binding of HK-2 nuclear proteins by putative upstream NF-Y, CCAAT, and NF-kappaB recognition sites was not observed. The identification of Sp1 and Sp3 as principal mediators of HAS2 constitutive transcription augments recent findings identifying upstream promoter elements and provides further insights into the mechanism of HAS2 transcriptional activation