lipid metabolism to avoid excessive hepatic lipid droplet deposition. However, destruction of the oxygen gradient by hypoxia accelerates hepatic steatosis ( Birchmeier 2016 , Kietzmann 2017 , 2019 ). Hypoxia-inducible transcription factors (HIFs) are
Lei Yu, Haoran Wang, Xiaoxue Han, Honghui Liu, Dalong Zhu, Wenhuan Feng, Jinhui Wu and Yan Bi
Chisato Katoh, Tomohiro Osanai, Hirofumi Tomita and Ken Okumura
-constituting cells such as astrocytes. In this study, we investigated whether BNP expression is enhanced in cultured human astrocytoma cell line U373MG when exposed to hypoxia, and if so, what signaling pathway is involved. We also examined whether endogenous BNP
Masami Hayashi, Masahiro Sakata, Takashi Takeda, Toshiya Yamamoto, Yoko Okamoto, Kenjiro Sawada, Akiko Kimura, Ryoko Minekawa, Masahiro Tahara, Keiichi Tasaka and Yuji Murata
response to oxygen deficiency in this organ. However, the precise mechanism regulating GLUT1 expression during placentation has not been fully clarified. Heterodimeric hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that mediates
Charles A Ducsay and Dean A Myers
by hypoxia. As such, NO represents a potential mechanism for changes in steroidogenesis in response to hypoxia. This review will focus on the role of NO in the regulation of steroidogenesis and the potential interaction of NO production and hypoxia
Daisuke Fujita, Akiko Tanabe, Tatsuharu Sekijima, Hekiko Soen, Keijirou Narahara, Yoshiki Yamashita, Yoshito Terai, Hideki Kamegai and Masahide Ohmichi
pregnancy. They demonstrated that the placenta develops in conditions of physiological hypoxia, in which the local oxygen concentration is as low as 1–2% during the first trimester. A significant increase was observed for placental PO 2 values measured at
PS Leung, SY Lam and ML Fung
In the present study, the effects of chronic hypoxia on the expression and localization of angiotensin II (Ang II) receptors are investigated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and by immunohistochemistry. The effect of chronic hypoxia on the carotid body chemoreceptor activity was also examined by in vitro electrophysiology. Results from RT-PCR revealed that chronic hypoxia exhibited differential effects on the gene expression of Ang II receptors, namely AT(1) and AT(2), in the carotid body. The mRNA expression for subtypes of the AT(1) receptor, AT(1a) and AT(1b), was significantly increased in the carotid body with chronic hypoxia. To further investigate the localization of the AT(1) receptor, an immunohistochemical study was performed. The results showed that AT(1) receptor immunoreactivity was found in lobules of glomus cells in the carotid body and the immunoreactivity was more intense in chronic hypoxia than in normoxic controls. In vitro electrophysiological studies consistently demonstrated that chronic hypoxia enhanced the AT(1) receptor-mediated excitation of carotid body chemoreceptor activity. These data suggest that chronic hypoxia upregulates the transcriptional and post-transcriptional expression of AT(1) receptors in the rat carotid body. The upregulation of the expression also enhances AT(1) receptor-mediated excitation of the carotid body afferent activity. This might be important in the modulation of cardiorespiratory functions as well as fluid and electrolyte homeostasis during chronic hypoxia.
M Tucci, K Nygard, BV Tanswell, HW Farber, DJ Hill and VK Han
Endothelial cells (EC) are hypoxia-tolerant and their capacity to proliferate in low oxygen tension is essential to maintain vascular endothelium integrity. The present study addresses whether hypoxia alters the expression of insulin-like growth factor (IGF) and IGF binding protein (IGFBP) genes in bovine aortic EC (BAEC) and bovine pulmonary artery EC (BPAEC). EC were cultured in normoxic (21%) conditions and exposed to 0% oxygen for 24, 48, or 72 h; some cells were reoxygenated by exposure to 21% oxygen for 24 or 48 h following hypoxia. IGF-I peptide and mRNA levels were very low in both cell types, and decreased further with exposure to hypoxia. Ligand blotting showed that both cell types synthesized 24 kDa (IGFBP-4), 30 kDa (IGFBP-5 and/or IGFBP-6), 43 kDa and 48 kDa IGFBPs (IGFBP-3 glycosylation variants). IGFBP-4 was the predominant IGFBP expressed by both cell types and did not change with exposure to hypoxia. Hypoxia caused a significant increase in IGFBP-3 secretion in BPAEC but not in BAEC. IGFBP-3 stable mRNA levels in BPAEC were increased correspondingly. IGFBP-5 was expressed only in BAEC and decreased with exposure to hypoxia. IGFBP-6 mRNA expression was low and increased in both cell types with exposure to hypoxia. These results demonstrate that EC IGFBP baseline expression as well as its expression in hypoxia vary in different vascular beds and suggest that the IGFBPs may be the dominant paracrine regulators of proliferation of EC as well as maintenance of endothelium integrity during hypoxia.
A Baldysiak-Figiel, GK Lang, J Kampmeier and GE Lang
Ocular diseases such as proliferative diabetic retinopathy are the major cause of blindness in industrialized countries. The main pathologic features of these diseases are hypoxia and overproduction of growth factors resulting in pathologic proliferation of endothelial cells and new vessel formation. Particularly, hypoxia and growth factors, such as VEGF, IGF-1, bFGF and TGF beta(2), show a complex interaction in the onset and progression of the diseases. Therefore, to date, most therapeutic strategies for proliferative retinopathies have targeted proliferation of endothelial cells evoked by growth factors. Recently, a synthetic analog of somatostatin, octreotide, has been shown to inhibit the proliferation of various cells in vitro, including endothelial cells. In this study, we have investigated the proliferative response of bovine retinal endothelial cells (BREC) to growth factors under hypoxic conditions and the modulation by octreotide. We found a dose-dependent increase of cell proliferation with VEGF, IGF-1 and bFGF, and inhibition of hypoxia-induced cell proliferation with TGF beta(2). Moreover, growth factor-induced, but not hypoxia-induced, cell proliferation was attenuated in the presence of octreotide. In contrast, TGF beta(2) abolished hypoxia-induced BREC proliferation. Similar to octreotide BIM23027, a somatastatin receptor subtype 2 (SSTR2) receptor agonist was able to attenuate the growth factor-induced proliferation of BREC expressing mRNA and protein for SSTR2. Therefore, we postulate that octreotide exerts its effects mainly through binding to the SSTR2. Taken together, our findings point to octreotide as a promising candidate for the treatment of eye disorders involving growth factor-dependent proliferation of endothelial cells.
A Aversa, S Basciani, P Visca, M Arizzi, L Gnessi, G Frajese and A Fabbri
Platelet-derived growth factor (PDGF) overactivity has been implicated in atherosclerosis and several fibrotic conditions including lung and kidney fibrosis, liver cirrhosis and myelofibrosis. Low oxygen tension (hypoxia) is a known stimulus for transcriptional induction of PDGF ligand and receptor genes in different tissues. We studied the expression and localization of PDGF-A, PDGF-B, and PDGF receptor (PDGFR)-alpha and -beta subunits in adult rat isolated corpus cavernosum (CC) under generalized transient hypoxia (pO(2) 10%) in comparison with normoxic conditions. Semi-quantitative RT-PCR analysis of mRNA extracted from rat penis showed higher amounts of PDGF-A, PDGF-B and PDGFR-beta mRNA transcripts in hypoxic versus normoxic animals. The immunohistochemical analysis showed that the localization of PDGF subunits and PDGFR-beta was confined to the cytoplasm of the perivascular smooth muscle cells, endothelium and trabecular fibroblasts. Our findings indicate that transient low oxygen tension induces PDGF overexpression in rat CC, which in the long term may lead to an increase of connective tissue production. We suggest that a local impairment of the PDGF/PDGFR system may contribute to CC fibrosis, which is an established cause of erectile dysfunction in man.
S S Jonker and S Louey
, these levels are more than 25 times higher than in the prepartum period but then decline soon after ( Velaphi et al . 2007 ). Fetal hypoxia and cortisol can both increase circulating plasma renin activity (PRA) and AII levels ( Broughton Pipkin et al