p38 MAP Kinase Regulates Stem Cell Apoptosis in Human Hematopoietic Failure

Zhou, Li; Opalinska, Joanna; Verma, Amit

doi:10.4161/cc.6.5.3921

Cited by 43 publications

(43 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, activation of p38 has been implicated in BM suppression in various pathological conditions, including aplastic anemia and myelodysplastic syndromes (118,175). Furthermore, recently, it was shown that mutation of the ATM gene and knockout of the FoxO3 gene induced premature senescence/exhaustion of HSCs (69,112,149).…”

Section: P38mentioning

confidence: 99%

Hematopoietic Stem Cell Injury Induced by Ionizing Radiation

Shao

Luo

Zhou

2014

Antioxidants & Redox Signaling

265

218

View full text Add to dashboard Cite

Significance: Exposure to ionizing radiation (IR) as the result of nuclear accidents or terrorist attacks is a significant threat and a major medical concern. Hematopoietic stem cell (HSC) injury is the primary cause of death after accidental or intentional exposure to a moderate or high dose of IR. Protecting HSCs from IR should be a primary goal in the development of novel medical countermeasures against radiation. Recent Advances: Significant progress has been made in our understanding of the mechanisms by which IR causes HSC damage. The mechanisms include (i) induction of HSC apoptosis via the p53-Puma pathway; (ii) promotion of HSC differentiation via the activation of the G-CSF/Stat3/BATF-dependent differentiation checkpoint; (iii) induction of HSC senescence via the ROS-p38 pathway; and (iv) damage to the HSC niche. Critical Issues: Induction of apoptosis in HSCs and hematopoietic progenitor cells is primarily responsible for IR-induced acute bone marrow (BM) injury. Long-term BM suppression caused by IR is mainly attributable to the induction of HSC senescence. However, the promotion of HSC differentiation and damage to the HSC niche can contribute to both the acute and long-term effects of IR on the hematopoietic system. Future Directions: In this review, we have summarized a number of recent findings that provide new insights into the mechanisms whereby IR damages HSCs. These findings will provide new opportunities for developing a mechanism-based strategy to prevent and/or mitigate IR-induced BM suppression.

show abstract

Section: P38mentioning

confidence: 99%

Hematopoietic Stem Cell Injury Induced by Ionizing Radiation

Shao

Luo

Zhou

2014

Antioxidants & Redox Signaling

265

218

View full text Add to dashboard Cite

show abstract

“…1 Unfortunately, the preclinical evaluation of drugs in MM, although very helpful in functionally defining important pathways, only rarely correlates with clinical activity in MM. Among recently approved drugs, thalidomide and lenalidomide have marginal activity in preclinical models of MM, and bortezomib, although very active in these models, has similar preclinical activity in models of other cancers that, in contrast, do not show clinical response.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…1 Moreover, a small-molecule inhibitor, SCIO-463 of the p38 MAP kinase pathway, improves hematopoiesis in myelodysplastic syndrome (MDS) progenitors in vitro. 1 The elegant experiments by Zhou et al extend their study of TGF-␤ signaling in MDS and show the constitutive downstream activation of smad2 in MDS bone marrow precursors and its overexpression in MDS-derived CD34 ϩ cells. Suppression of TGF-␤ activity by shRNA down-regulation of TGF-␤ receptor I kinase (TBRI) as well as pharmacologic inhibition of TBRI (alk5) by a smallmolecule inhibitor (SD-208) leads to a reversal of this TGF-␤-mediated inhibition of hematopoiesis in MDS.…”

mentioning

confidence: 99%

“…1 Ineffective hematopoiesis in MDS may be intrinsic to dysregulated gene expression as well as resulting from dysfunctional cell-to-cell contacts within the stromal microenvironment. 2,3 TGF-␤ overactivation in MDS leads to altered stromal cytokine expression with decreased IL-7 and decreased B-cell proliferation 4 and enhanced IL-1␤ and TNF␣ associated with increased stromal IL-6, IL-8, and IL-32 expression.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Unlocking the dysplasia puzzle

Abboud¹

2008

Blood

View full text Add to dashboard Cite

The cross-talk between ROS and p38MAPKα in the Ex Vivo expanded human umbilical cord blood CD133+ cells

Zou

Lou

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

View full text Add to dashboard Cite

This study investigated the correlation between and compared the effects of reactive oxygen species (ROS) and p38 mitogen-activated protein kinase α (p38MAPKα) in the ex vivo expanded umbilical cord blood (hUCB) CD133(+) cells. hUCB CD133(+) cells were cultured in the hematopoietic stem cells (HSCs) culture medium with N-acetylcysteine (NAC, an anti-oxidant), p38MAPKα-specific inhibitor (SB203580) or their combination. The levels of ROS and expression of phosphorylated p38MAPKα (p-p38) in CD133(+) cells were flow cytometrically detected. The efficacy of ex vivo expansion was evaluated by the density of CD133(+) cell sub-group colony-forming cells (CFC) and cobblestone area-forming cells (CAFC) assay. Our results showed decreased ROS levels in NAC, SB203580, and their combination treatment groups were almost 37%, 48%, and 85%, respectively. Furthermore, SB203580 abrogated the activation of p38MAPKα more obviously than NAC. Moreover, the CD133(+) cells in SB203580 treatment group had a 21.93±1.36-fold increase, and 14.50±1.19-fold increase in NAC treatment group, but only 10.13±0.57-fold increase in control group. In addition, SB203580 treatment led a higher level increase in the number of CFU and CAFC than NAC did. These findings suggested that, in expanded CD133(+) cells, ROS activates p38MAPKα, which, in turn, induces ROS production, and p38MAPKα might be the most suitable regulator in ROS-p38MAPKα pathway for the promotion of HSCs ex vivo expansion.

show abstract

p38 MAP Kinase Regulates Stem Cell Apoptosis in Human Hematopoietic Failure

Cited by 43 publications

References 33 publications

Hematopoietic Stem Cell Injury Induced by Ionizing Radiation

Hematopoietic Stem Cell Injury Induced by Ionizing Radiation

Unlocking the dysplasia puzzle

The cross-talk between ROS and p38MAPKα in the Ex Vivo expanded human umbilical cord blood CD133+ cells

Contact Info

Product

Resources

About