Effects of Hypoxia on Morphological and Biochemical Characteristics of Renal Epithelial Cell and Tubule Cultures

Abstract

Apoptotic cell death plays an important role in the pathogenesis of renal atrophy in diseases of the kidney involving chronic mild ischemia. The present study constitutes an in vitro model of these diseases and assesses the modes of cell death involved after hypoxic treatment of renal epithelium. Cultures of MDCK cells or primary cultures of rat renal parenchymal tubules were treated in either a physiological or a hypoxic atmosphere. Cultures were collected before treatment and at 24 h and 48 h, for morphological and biochemical studies. Both apoptosis and necrosis were observed at significantly increased levels by 48 h of hypoxia in the MDCK cell cultures. DNA gel electrophoresis patterns supported these findings. Experiments using tubule cultures demonstrated that, during the 48 h of study, tubular epithelial cells in the center of the control tubule structures died by apoptosis, possibly as a result of mild oxygen and/or nutrient depletion. With added hypoxic treatment, however, the entire tubule structure became necrotic. Results are similar to those found during in vivo studies, thus providing in vitro models that may be developed further to define factors in the pathogenesis of some renal diseases.

Maternal Smoking, Intrauterine Growth Restriction, and Placental Apoptosis

“…The pro- cess may be influenced by different stimuli, both physiological and nonphysiological [37]. Nicotine has been related to the inhibition of apoptosis in cell cultures [8,9], while hypoxia has been shown to induce apoptosis [6,38,39]. Enhancement of apoptosis by hypoxia has also been demonstrated in cultured human trophoblasts, while addition of epidermal growth factor (EGF) to the cultures lowers the level of apoptosis [39], suggesting that EGF may protect against apoptosis induced by hypoxia.…”

The Membrane-bound Form of Heparin-binding Epidermal Growth Factor-like Growth Factor Promotes Survival of Cultured Renal Epithelial Cells

“…As with other cells, the epithelial cells of the kidney are susceptible to injury by toxins or ischemia, which can predispose to either necrotic or apoptotic cell death (1)(2)(3)(4)(5)(6). Accumulating evidence indicates that locally produced growth factors may serve as mediators of regeneration of renal epithelial cells following acute injuries (1,2,7).…”

Induction of apoptotic cell death by pancreatitis‐associated ascitic fluid in Madin‐Darby canine kidney cells

“…One is a non-specific mechanism such as hypoxic stress as reported previously on MDCK cells [22]. As the existence of interfered substance(s) against mitochondrial respiration in PAAF has been documented by several researchers [8,31,32], the possibility cannot be neglected that apoptosis is induced by putative substance(s) interfering mitochondrial respiration.…”

“…The MDCK cell is the established cell line of normal distal tubular cells from canine renal parenchyma, and it has been already reported that apoptotic cell death is inducible on this cell line by hypoxia [22], infection of influenza viruses [23], or the treatment with TGF-fl [24] or toxins such as ricin.…”