Cisplatin effects on F-actin and matrix proteins precede renal tubular cell detachment and apoptosis in vitro

Kruidering, Marieke; B, van de Water; Zhan, Yi; Baelde, Hans J.; Heer, Emile de; Gj, Mulder; Jl, Stevens; Jf, Nagelkerke

doi:10.1038/sj.cdd.4400392

Cited by 79 publications

(76 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17 The resulting pattern at the reticular lamina reported in Burns and Corwin 17 is reminiscent of that reported here following cisplatin treatment (Figure 5c), consistent with cisplatin disrupting actin dynamics. [43][44][45] Our in vivo data show that phalangeal scars formed in aminoglycoside-treated cochleas are more actin-rich than those formed in cisplatin-treated cochleas (Figure 8), further suggesting that cisplatin impairs F-actin dynamics in the inner ear.…”

Section: Discussionmentioning

confidence: 99%

Live imaging the phagocytic activity of inner ear supporting cells in response to hair cell death

et al. 2015

View full text Add to dashboard Cite

Hearing loss and balance disorders affect millions of people worldwide. Sensory transduction in the inner ear requires both mechanosensory hair cells (HCs) and surrounding glia-like supporting cells (SCs). HCs are susceptible to death from aging, noise overexposure, and treatment with therapeutic drugs that have ototoxic side effects; these ototoxic drugs include the aminoglycoside antibiotics and the antineoplastic drug cisplatin. Although both classes of drugs are known to kill HCs, their effects on SCs are less well understood. Recent data indicate that SCs sense and respond to HC stress, and that their responses can influence HC death, survival, and phagocytosis. These responses to HC stress and death are critical to the health of the inner ear. Here we have used live confocal imaging of the adult mouse utricle, to examine the SC responses to HC death caused by aminoglycosides or cisplatin. Our data indicate that when HCs are killed by aminoglycosides, SCs efficiently remove HC corpses from the sensory epithelium in a process that includes constricting the apical portion of the HC after loss of membrane integrity. SCs then form a phagosome, which can completely engulf the remaining HC body, a phenomenon not previously reported in mammals. In contrast, cisplatin treatment results in accumulation of dead HCs in the sensory epithelium, accompanied by an increase in SC death. The surviving SCs constrict fewer HCs and display impaired phagocytosis. These data are supported by in vivo experiments, in which cochlear SCs show reduced capacity for scar formation in cisplatin-treated mice compared with those treated with aminoglycosides. Together, these data point to a broader defect in the ability of the cisplatin-treated SCs, to preserve tissue health in the mature mammalian inner ear. . 4 SCs perform many functions, including providing critical trophic factors, preventing excitotoxicity, and mediating regeneration in those systems (non-mammalian vertebrates) capable of replacing lost HCs. 5-11 When HCs die, SCs also preserve the integrity and function of the remaining tissue by forming scars and clearing dead HCs. 2,12-17 Maintaining a fluid barrier at the surface of the sensory epithelium after damage is necessary to preserve the electro-chemical gradient that drives HC depolarization and therefore sensory transduction after the onset of hearing (reviewed in Wangemann). 18 Several major stressors cause HC death, 19-22 including aging, noise trauma, and exposure to therapeutic drugs with ototoxic side effects. When a HC is killed by noise or aminoglycoside antibiotics, surrounding SCs form a filamentous actin (F-actin) cable that constricts the HC at its apex. 2,[12][13][14][15][16][17] This process separates the apical portion of the cell, including the stereocilia bundle, from the HC body and preserves a sealed reticular lamina. 23 In the chick utricle, following the apical constriction of dead HCs, the SCs engulf and phagocytose the remaining HC corpse. 15 Additional data from the chick indicate that the ototoxi...

show abstract

Section: Discussionmentioning

confidence: 99%

Live imaging the phagocytic activity of inner ear supporting cells in response to hair cell death

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Our studies demonstrated that Cap is potent in protecting against free radical damage induced by CDDP. CDDP gener- ates active oxygen species such as superoxide anion and hydroxyl radical 28,29) and stimulates renal lipid peroxidation. 23,[30][31][32] The free radical scavengers SOD are reported to provide partial protection against CDDP-induced structural and functional alteration in rats.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Capsaicin against Cisplatin-Induced Nephrotoxicity in Rats

Shimeda

Hirotani

Akimoto

et al. 2005

Biological & Pharmaceutical Bulletin

126

View full text Add to dashboard Cite

Cisplatin (cis-diaminedichloroplatinum II, CDDP) is extensively used for the treatment of several cancers. Its major side effect; namely, nephrotoxicity, is a dose-limiting factor in CDDP therapy.1) The exact mechanisms of nephrotoxicity induced by CDDP are still not fully elucidated. However, lipid peroxidation and free radical generation in the renal tubular cells have been suggested to be responsible for CDDP-induced renal failure.2) Zhang et al. showed that CDDP significantly depletes glutathione (GSH) and increases lipid peroxidation in the mitochondria prepared from the rat renal cortical slices.3) In addition, the activities of superoxide dismustase (SOD) and catalase in the rat kidney tissues are significantly suppressed by CDDP. 4)Capsaicin (Cap) is the major pungent ingredient of hot red peppers. It has been used as a tool in the study of pain sensations which are caused by stimulation of Cap receptor or vanilloid receptor 1, an ion channel protein expressed by nociceptive primary afferent neurons. 5,6) On the other hand, Cap potentially inhibits the peroxidation of various lipids [7][8][9][10] and generates reactive oxygen species in rat peritoneal macrophages.11) However, the mechanism responsible for the potent inhibitory effects of Cap on lipid peroxidation in vivo is still unclear.Several studies have examined the effects of decreased lipid peroxidation and nephrotoxicity induced by CDDP using various agents including antioxidants. [12][13][14] The purpose of the present study was to investigate whether the administration of Cap exerts any protective effect against cisplatin-induced lipid peroxidation and nephrotoxicity in rats. MATERIALS AND METHODS ChemicalsCap with a purity of 98.6% was kindly supplied by Maruishi Pharmaceutical Co., Ltd. (Osaka, Japan). CDDP was purchased from Sigma (MO, U.S.A.). All other chemicals and reagents used were of analytical grade.Animals Male Sprague-Dawley rats weighing 200 to 250 g were purchased from Nippon SLC Inc. (Shizuoka, Japan). The rats had free access to standard rat chow and water ad libitum, were individually housed in metal cages, and kept in a room maintained at 23Ϯ2°C with a 12 h/12 h light/dark cycle. The study adhered to the guidelines of Osaka University of Pharmaceutical Sciences for the experimental use of animals.Animal Treatments The rats were divided at random into 4 groups of 4 or 5 animals each. The first group (control) received a vehicle (5% carboxymethyl cellulose sodium solution (CMC-Na), 5 ml/kg body wt., p.o.) used for Cap. The second group received Cap (10 mg/kg/d, p.o.) in 5% CMC-Na (5 ml/kg), and the third received 5% CMC-Na for 6 consecutive days injected with CDDP (5 mg/kg in physiological saline solution, i.p.). The fourth group received Cap (10 mg/kg/d, p.o.) in 5% CMC-Na for 6 consecutive days after CDDP injection (5 mg/kg, i.p.). For all groups, Cap or vehicle was given twice daily. The selected Cap concentration and the dose administration schedule without inducing any rat intestinal damage were chosen using data from our p...

show abstract

“…We next analysed the e ects of several inhibitors of MRC complexes I ± IV on ROS generation using inhibitor concentrations equal to or higher than those reported by others to inhibit the respective complexes in other cell types (Kruidering et al, 1997). The MRC 3,6,9,12,15,18,21,24 h and induction of MPT was detected as above.…”

Section: E Ects Of Mrc Inhibitors and Uncoupler On 4hpr-induced Ros Gmentioning

confidence: 99%

Implication of mitochondria-derived reactive oxygen species, cytochrome C and caspase-3 in N-(4-Hydroxyphenyl)retinamide-induced apoptosis in cervical carcinoma cells

et al. 1999

View full text Add to dashboard Cite

N-(4-Hydroxyphenyl)retinamide (4HPR) is currently used in cancer prevention and therapy trials. It is thought that its e ects result from induction of apoptosis. 4HPR-induced apoptosis in human cervical carcinoma C33A cells involves enhanced generation of reactive oxygen species (ROS). In this study we explored the mechanism by which 4HPR increases ROS and induces apoptosis in these cells. 4HPR induced cytochrome c release from mitochondria to cytoplasm, activated caspase-3, and caused a membrane permeability transition (MPT). All these 4HPR's e ects, as well as the induction of apoptosis, were inhibited by antioxidants, which decrease ROS. Thenoyltri¯uoroacetone, a mitochondrial respiratory chain (MRC) complex II inhibitor, and carbonylcyanide m-chlorophenyl hydrazone, which uncouples electron transfer and ATP synthesis and inhibits ROS generation by MRC, inhibited 4HPR-induced ROS generation very e ectively. Rotenone, an MRC complex I inhibitor was less e ective and azide, an MRC complex IV inhibitor, exhibited a marginal e ect. In contrast, antimycin A, an MRC complex III inhibitor, enhanced 4HPR-induced ROS generation. These ®ndings suggest that 4HPR enhances ROS generation by a ecting a target between complex II and complex III, presumably coenzyme Q. This e ect is followed by release of cytochrome c, increased caspase-3 activity, induction of MPT and eventual DNA fragmentation and cell death.

show abstract

Cisplatin effects on F-actin and matrix proteins precede renal tubular cell detachment and apoptosis in vitro

Cited by 79 publications

References 20 publications

Live imaging the phagocytic activity of inner ear supporting cells in response to hair cell death

Live imaging the phagocytic activity of inner ear supporting cells in response to hair cell death

Protective Effects of Capsaicin against Cisplatin-Induced Nephrotoxicity in Rats

Implication of mitochondria-derived reactive oxygen species, cytochrome C and caspase-3 in N-(4-Hydroxyphenyl)retinamide-induced apoptosis in cervical carcinoma cells

Contact Info

Product

Resources

About