Nitric Oxide and Apoptosis: Another Paradigm for the Double-Edged Role of Nitric Oxide

Dimmeler, Stefanie; Zeiher, Andreas M.

doi:10.1006/niox.1997.0133

Cited by 294 publications

(176 citation statements)

References 59 publications

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“…However, in nine of ten patients, increased numbers of CD68 ϩ macrophages were present in PL skin. In addition to the possibility that infiltrating macrophages are involved in clearing apoptotic cells (Savill, 1997), a direct involvement of macrophages in melanocyte killing, probably via the nitric oxide pathway (Dimmeler and Zeiher, 1997), cannot be ruled out. Using 3-morpholino-syndonimine (SIN-1) as a nitric oxide donor, it has been observed that nitric oxide induces detachment and apoptosis of melanocytes cultured on fibronectin-coated plates (K. Ivanova, Institute of Aerospace Medicine, Germany, personal communication, 1998).…”

Section: Figurementioning

confidence: 99%

Local Immune Response in Skin of Generalized Vitiligo Patients

Wijngaard

Wańkowicz-Kalińska

Poole

et al. 2000

Laboratory Investigation

219

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SUMMARY:In situ immune infiltrates in lesional, perilesional, and nonlesional skin biopsies from patients with vitiligo were analyzed by immunohistochemistry and compared with immune infiltrates found in the skin of normal healthy donors and relevant disease controls. An increased influx of activated skin-homing T cells and macrophages were seen in the perilesional biopsies. The overall percentages of cutaneous leukocyte-associated antigen-positive (CLA ϩ ) T cells were similar to those found in normal healthy donors. This is compatible with the similar expression of E-selectin. Most strikingly, however, the CLA ϩ T cells in perilesional skin were mainly clustered in the vicinity of disappearing melanocytes, and 60% to 66% of these interacting T cells expressed perforin and granzyme-B. The perforin ϩ /granzyme-B ϩ cells were not seen in locations different from that of disappearing melanocytes. Interestingly, the majority of the infiltrating T cells were HLA-DR/CD8 ϩ . Another hallmark of the present study is the focal expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR in the epidermis at the site of interaction between the immune infiltrates and the disappearing melanocytes. The data presented in this study are consistent with a major role for skin-homing T cells in the death of melanocytes seen in vitiligo. (Lab Invest 2000, 80:1299-1309.

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Section: Figurementioning

confidence: 99%

Local Immune Response in Skin of Generalized Vitiligo Patients

Wijngaard

Wańkowicz-Kalińska

Poole

et al. 2000

Laboratory Investigation

219

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“…NO-mediated apoptosis is often observed in such cases. [2][3][4] NO has cytotoxic effects, including reactions with proteins and nucleic acids. NO-induced apoptosis was generally considered to be mediated by DNA or mitochondrial damages; however, the cascade of the cell death has not been clarified.…”

Section: Introductionmentioning

confidence: 99%

hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria

et al. 2004

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We reported that the endoplasmic reticulum (ER) stress pathway involving CHOP, a member of the C/EBP transcription factor family, plays a key role in nitric oxide (NO)-mediated apoptosis of macrophages and pancreatic b cells. We also showed that the cytosolic chaperone pair of hsp70 and dj1 (hsp40/hdj-1) or dj2 (HSDJ/hdj-2) prevents NO-mediated apoptosis upstream of cytochrome c release from mitochondria. To analyze roles of the chaperone pair in preventing apoptosis, RAW 264.7 macrophages stably expressing hsp70 and dj1 or dj2 were established. The chaperone pair prevented LPS/IFN-c-induced and NO-mediated apoptosis downstream of CHOP induction. hsp70 mutant protein lacking the ATPase domain or the C-terminal EEVD sequence were not effective in preventing CHOP-induced apoptosis. A mutant dj2 lacking the C-terminal prenylation CaaX motif, was also not effective. When wild-type RAW 264.7 cells were treated with LPS/IFN-c, NOmediated apoptosis was induced, and proapoptotic Bcl-2 family protein Bax was translocated from cytosol to mitochondria. This translocation was prevented in cells stably expressing hsp70/dj2, and in CHOP knockout cells. Overexpression of CHOP in wild-type cells also induced translocation of Bax and this translocation was prevented in cells expressing hsp70/dj2. CHOP-induced apoptosis was prevented by Bax knock-down. Coimmunoprecipitation experiments showed that Bax interacts with both hsp70 and dj1/dj2. ATPase domain of hsp70 was necessary for the binding with Bax. These findings indicate that CHOP-induced apoptosis is mediated by translocation of Bax from the cytosol to the mitochondria, and hsp70/dj1 or dj2 chaperone pair prevents apoptosis by interacting with Bax and preventing translocation to the mitochondria.

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“…[3][4][5][6] At first glance, pro-apoptotic effects seem to be associated with pathophysiological conditions and with high output NO production by iNOS, whereas the continuous release of low output NO via constitutive NOS would lead to protection. The present review will try to summarize the effects of NO on human leukemic cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms involved in the pro- and anti-apoptotic role of NO in human leukemia

2000

Leukemia

129

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Nitric Oxide and Apoptosis: Another Paradigm for the Double-Edged Role of Nitric Oxide

Cited by 294 publications

References 59 publications

Local Immune Response in Skin of Generalized Vitiligo Patients

Local Immune Response in Skin of Generalized Vitiligo Patients

hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria

Mechanisms involved in the pro- and anti-apoptotic role of NO in human leukemia

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