Involvement of cathepsin B in mitochondrial apoptosis by p-phenylenediamine under ambient UV radiation

Goyal, Shruti; Amar, Saroj Kumar; Dubey, Divya; Pal, Mahendra; Singh, Jyoti; Verma, Ankit; Kushwaha, Hari Narayan; Ray, Ratan Singh

doi:10.1016/j.jhazmat.2015.07.032

Cited by 32 publications

(17 citation statements)

References 31 publications

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“…Cathepsins represent the largest group of proteolytic enzymes in the lysosome, wherein CTSB and CTSD are two abundant lysosomal proteases. 23, 39 Since the maturation (activation) of cathepsin proteases requires acidification, the altered pH ultimately resulted in greatly reduced protein degradation. 40 As shown in Figure 6b, Pb interfered with the maturation of CTSB and CTSD in rPT cells, further verifying that Pb inhibited the lysosomal function by affecting the maturation of selected proteases.…”

Section: Discussionmentioning

confidence: 99%

Autophagy blockade and lysosomal membrane permeabilization contribute to lead-induced nephrotoxicity in primary rat proximal tubular cells

et al. 2017

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Lead (Pb) is a known nephrotoxicant that causes damage to proximal tubular cells. Autophagy has an important protective role in various renal injuries, but the role of autophagy in Pb-elicited nephrotoxicity remains largely unknown. In this study, Pb promoted the accumulation of autophagosomes in primary rat proximal tubular (rPT) cells, and subsequent findings revealed that this autophagosome accumulation was caused by the inhibition of autophagic flux. Moreover, Pb exposure did not affect the autophagosome–lysosome fusion in rPT cells. Next, we found that Pb caused lysosomal alkalinization, may be through suppression of two V-ATPase subunits. Simultaneously, Pb inhibited lysosomal degradation capacity by affecting the maturation of cathepsin B (CTSB) and cathepsin D (CTSD). Furthermore, translocation of CTSB and CTSD from lysosome to cytoplasm was observed in this study, suggesting that lysosomal membrane permeabilization (LMP) occurred in Pb-exposed rPT cells. Meanwhile, Pb-induced caspase-3 activation and apoptosis were significantly but not completely inhibited by CTSB inhibitor (CA 074) and CTSD inhibitor (pepstatin A), respectively, demonstrating that LMP-induced lysosomal enzyme release was involved in Pb-induced apoptosis in rPT cells. In conclusion, Pb-mediated autophagy blockade in rPT cells is attributed to the impairment of lysosomal function. Both inhibition of autophagic flux and LMP-mediated apoptosis contribute to Pb-induced nephrotoxicity in rPT cells.

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Section: Discussionmentioning

confidence: 99%

Autophagy blockade and lysosomal membrane permeabilization contribute to lead-induced nephrotoxicity in primary rat proximal tubular cells

et al. 2017

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“…As seen in Fig. , SBNs are rich in mitochondria; UV radiation damages mitochondria (Goyal et al, ). The high density of ICNs on the cornea makes it more efficient for them to shed their termini and extend new axons.…”

Section: Sbns Continually Remodel and Grow During Homeostasismentioning

confidence: 99%

Corneal epithelial cells function as surrogate Schwann cells for their sensory nerves

Stepp

Tadvalkar

Hakh

et al. 2016

Glia

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The eye is innervated by neurons derived from both the central nervous system and peripheral nervous system. While much is known about retinal neurobiology and phototransduction, less attention has been paid to the innervation of the eye by the PNS and the roles it plays in maintaining a functioning visual system. The ophthalmic branch of the trigeminal ganglion contains somas of neurons that innervate the cornea. These nerves provide sensory functions for the cornea and are referred to as intraepithelial corneal nerves (ICNs) consisting of subbasal nerves and their associated intraepithelial nerve terminals. ICNs project for several millimeters within the corneal epithelium without Schwann cell support. Here, we present evidence for the hypothesis that corneal epithelial cells function as glial cells to support the ICNs. Much of the data supporting this hypothesis is derived from studies of corneal development and the reinnervation of the ICNs in the rodent and rabbit cornea after superficial wounds. Corneal epithelial cells activate in response to injury via mechanisms similar to those induced in Schwann cells during Wallarian Degeneration. Corneal epithelial cells phagocytize distal axon fragments within hours of ICN crush wounds. During aging, the proteins, lipids, and mitochondria within the ICNs become damaged in a process exacerbated by UV light. We propose that ICNs shed their aged and damaged termini and continuously elongate to maintain their density. Available evidence points to new unexpected roles for corneal epithelial cells functioning as surrogate Schwann cells for the ICNs during homeostasis and in response to injury.

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“…CTSB-dependent Bid cleavage, as well as tBid and Bax translocation to mitochondrial outer membrane have been observed in in vivo and cell culture studies [53–56]. Bcl2 and Bcl-xL may also be involved in MOMP [53–56]. Extensive CTSB release, however, can digest proteins indiscriminately to directly induce cell death [46].…”

Section: Ctsb Release Induces Mitochondrial Outer Membrane Permeabilimentioning

confidence: 99%

Dysfunction of Membrane Trafficking Leads to Ischemia-Reperfusion Injury After Transient Cerebral Ischemia

Liu

2017

Transl. Stroke Res.

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Neurons require an extraordinarily high level of membrane trafficking activities because of enriched axonal terminals and dendritic branches. For that reason, defects in the membrane trafficking pathway are a hallmark of most, and may be all, neurodegenerative disorders. A major cellular membrane trafficking pathway is the Golgi apparatus (Golgi hereafter)-late endosome-lysosome axis for supplying lysosomal enzymes. This pathway is regulated by N-ethylmaleimide-sensitive factor (NSF) ATPase. This review article is to discuss a novel hypothesis that brain ischemia inactivates NSF ATPase, resulting in a cascade of events of disruption of the Golgi-endosome-lysosome pathway, release of cathepsin B (CTSB), and induction of mitochondrial outer membrane permeabilization (MOMP) during the postischemic phase. This hypothesis is supported by recent studies demonstrating that NSF is trapped into inactive protein aggregates in neurons destined to die after brain ischemia. Consequently, Golgi, transport vesicles (TVs), and late endosomes (LEs) are accumulated and damaged, which is followed by CTSB release from these damaged structures. Moderate release of CTSB cleaves Bax-like BH3 protein (Bid) to become active truncated Bid (tBid). Active tBid is then translocated to the mitochondrial outer membrane, resulting in oligomerization of BCL2-associated X protein (Bax) forming the mitochondrial outer membrane pores, and releasing mitochondrial intramembranous proteins. Extensive CTSB release, however, can digest cellular proteins indiscriminately to induce cell death. Based on these new observations, we propose a novel hypothesis, i.e., brain ischemia leads to NSF inactivation, resulting in a massive buildup of damaged Golgi, TVs and LEs, fatal release of CTSB, induction of MOMP, and eventually brain ischemia-reperfusion injury.

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Involvement of cathepsin B in mitochondrial apoptosis by p-phenylenediamine under ambient UV radiation

Cited by 32 publications

References 31 publications

Autophagy blockade and lysosomal membrane permeabilization contribute to lead-induced nephrotoxicity in primary rat proximal tubular cells

Autophagy blockade and lysosomal membrane permeabilization contribute to lead-induced nephrotoxicity in primary rat proximal tubular cells

Corneal epithelial cells function as surrogate Schwann cells for their sensory nerves

Dysfunction of Membrane Trafficking Leads to Ischemia-Reperfusion Injury After Transient Cerebral Ischemia

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