Role of heat shock protein 60 (HSP60) on paraquat intoxication

Kaetsu, Akihiko; Fukushima, Tetsuhito; Inoue, Seigou; Lim, Heejin; Moriyama, Masaki

doi:10.1002/jat.774

Cited by 15 publications

(11 citation statements)

References 32 publications

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“…Moreover, paraquat had no effect on lipid peroxidation level of the lung. This finding is in agreement with Kaetsu et al (2001) who showed that the concentration of malondialdehyde in rat lung homogenate did not change after 14 and 28 days exposure of paraquat. Also, previous studies of chronic administration of paraquat showed that paraquat can cause morphological change without an increase of lipid peroxidation (Saunier et al, 1982;Kifune et al, 1990).…”

Section: Discussionsupporting

confidence: 95%

Antifibrotic effect of captopril and enalapril on paraquat‐induced lung fibrosis in rats

Ghazi‐Khansari

Mohammadi-Karakani

Sotoudeh

et al. 2007

J of Applied Toxicology

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Although different treatment modalities have been implemented for pulmonary fibrosis, the results have not been promising and these conditions have been considered untreatable and irreversible. Thus, a plethora of new drugs has been tried for the control of this condition in recent years. This study examined the effects of two angiotensin-converting enzyme inhibitors, captopril and enalapril, on paraquat-induced pulmonary fibrosis in rats, through biochemical and histopathological parameters. Male albino Wistar rats were divided into eight groups (n = 4-5 each), including control, paraquat, captopril alone, captopril treatment and pre-treatment, enalapril alone, enalapril treatment and pre-treatment. After 21 days of treatment, the lungs were removed and the levels of hydroxyproline, glutathione and lipid peroxidation were determined. Angiotensin-converting enzyme inhibitors showed no effect on glutathione and lipid peroxidation. The results also demonstrated that captopril and enalapril improved pulmonary fibrosis as shown by histopathology, as well as a decreased content of hydroxyproline (P < 0.001) in the lung tissue. In conclusion, the present findings suggest that the antifibrotic effect of these drugs may be related to the inhibition of angiotensin-converting enzyme.

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Section: Discussionsupporting

confidence: 95%

Antifibrotic effect of captopril and enalapril on paraquat‐induced lung fibrosis in rats

Ghazi‐Khansari

Mohammadi-Karakani

Sotoudeh

et al. 2007

J of Applied Toxicology

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“…While less is known regarding the specific role of Hsp60 in acute lung injury, Hsp60 has been detected in the bronchial epithelium of patients with asthma (124), nonhuman primates following ozone exposure (77), and human pulmonary microvascular endothelial cells following both heat shock and heavy metal exposure (125). Furthermore, in vivo studies suggest that Hsp60 expression has been shown to ameliorate the progression to pulmonary fibrosis induced by paraquat intoxication (126). Collectively, these studies therefore suggest that Hsp60 confers stress tolerance in the lung.…”

Section: Hsp60mentioning

confidence: 99%

Heat shock response and acute lung injury☆

Wheeler

Wong

2007

Free Radical Biology and Medicine

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All cells respond to stress through the activation of primitive, evolutionarily conserved genetic programs that maintain homeostasis and assure cell survival. Stress adaptation, which is known in the literature by a myriad of terms, including tolerance, desensitization, conditioning, and reprogramming, is a common paradigm found throughout nature, in which a primary exposure of a cell or organism to a stressful stimulus (e.g., heat) results in an adaptive response by which a second exposure to the same stimulus produces a minimal response. More interesting is the phenomenon of cross-tolerance, by which a primary exposure to a stressful stimulus results in an adaptive response whereby the cell or organism is resistant to a subsequent stress that is different from the initial stress (i.e. exposure to heat stress leading to resistance to oxidant stress). The heat shock response is one of the more commonly described examples of stress adaptation and is characterized by the rapid expression of a unique group of proteins collectively known as heat shock proteins (also commonly referred to as stress proteins). The expression of heat shock proteins is well described in both whole lungs and in specific lung cells from a variety of species and in response to a variety of stressors. More importantly, in vitro data, as well as data from various animal models of acute lung injury, demonstrate that heat shock proteins, especially Hsp27, Hsp32, Hsp60, and Hsp70 have an important cytoprotective role during lung inflammation and injury.

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“…The phasic augmentation of the protein level of HSP60 or HSP70 in the ventrolateral medulla during Mev intoxication revealed by complementary proteomic and Western blot analyses further corroborated these physiological results. In this regard, rat lung mitochondria exhibit a prolonged increase in HSP60 expression when exposed to paraquat, which prevents the progression of pulmonary fibrosis induced by this organophosphate poison (53). Augmentation of HSP70 expression in the ventrolateral medulla is causally and temporally related to its antagonism of circulatory suppression during endotoxemia (14,20).…”

Section: Hsp60 Also Interacts With the Bax/bcl-2/cytochrome C/caspasementioning

confidence: 99%

Heat Shock Protein 60 or 70 Activates Nitric-oxide Synthase (NOS) I- and Inhibits NOS II-associated Signaling and Depresses the Mitochondrial Apoptotic Cascade during Brain Stem Death

Chan

Cheng

Chou

et al. 2007

Journal of Biological Chemistry

108

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The cellular and molecular basis of brain stem death remains an enigma. As the origin of a "life-and-death" signal that reflects the progression toward brain stem death, the rostral ventrolateral medulla (RVLM) is a suitable neural substrate for mechanistic delineation of this phenomenon. Here, we evaluated the hypothesis that heat shock proteins (HSPs) play a neuroprotective role in the RVLM during brain stem death and delineated the underlying mechanisms, using a clinically relevant animal model that employed the organophosphate pesticide mevinphos (Mev) as the experimental insult. In Sprague-Dawley rats, proteomic, Western blot, and real-time PCR analyses demonstrated that Mev induced de novo synthesis of HSP60 or HSP70 in the RVLM without affecting HSP90 level. Loss-of-function manipulations of HSP60 or HSP70 in the RVLM using antiserum or antisense oligonucleotide potentiated Mev-elicited cardiovascular depression alongside reduced nitric-oxide synthase (NOS) I/protein kinase G signaling, enhanced NOS II/peroxynitrite cascade, intensified nucleosomal DNA fragmentation, elevated cytoplasmic histone-associated DNA fragments or activated caspase-3, and augmented the cytochrome c/caspase-3 cascade of apoptotic signaling in the RVLM. Coimmunoprecipitation experiments further revealed a progressive increase in the complex formed between HSP60 and mitochondrial or cytosolic Bax or mitochondrial Bcl-2 during Mev intoxication, alongside a dissociation of the cytosolic HSP60-Bcl-2 complex. We conclude that HSP60 and HSP70 confer neuroprotection against Mev intoxication by ameliorating cardiovascular depression via an anti-apoptotic action in the RVLM. The possible underlying intracellular processes include enhancing NOS I/protein kinase G signaling and inhibiting the NOS II/peroxynitrite cascade. In addition, HSP60 exerts its effects against apoptosis by blunting Mev-induced activation of the Bax/cytochrome c/caspase-3 cascade.Whereas brain stem death is currently the clinical definition of death in many countries (1, 2), the cellular and molecular underpinnings of this phenomenon of paramount medical importance are wanting. The invariable prognosis, that asystole takes place within hours or days after the diagnosis of brain stem death (3), strongly suggests that permanent impairment of the brain stem cardiovascular regulatory machinery should precede death. It is therefore intriguing that our laboratory demonstrated previously that a common denominator exists among patients who succumbed to systemic inflammatory response syndrome (4), severe brain injury (5), or organophosphate poisoning (6). We found that a dramatic reduction or loss of the power density of the low frequency (LF) 3 component (0.04 -0.15 Hz in human) in the systemic arterial pressure (SAP) spectrum, which reflects failure of brain stem cardiovascular regulatory functions, invariably precedes death. We further established that this "life-and-death" signal takes origin from the rostral ventrolateral medulla (RVLM) (7), the brain stem site responsible ...

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Role of heat shock protein 60 (HSP60) on paraquat intoxication

Cited by 15 publications

References 32 publications

Antifibrotic effect of captopril and enalapril on paraquat‐induced lung fibrosis in rats

Antifibrotic effect of captopril and enalapril on paraquat‐induced lung fibrosis in rats

Heat shock response and acute lung injury☆

Heat Shock Protein 60 or 70 Activates Nitric-oxide Synthase (NOS) I- and Inhibits NOS II-associated Signaling and Depresses the Mitochondrial Apoptotic Cascade during Brain Stem Death

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