Tumor suppressor p53 is a direct transcriptional activator of the human bax gene

Miyashita, Toshiyuki; Reed, John C.

doi:10.1016/0092-8674(95)90412-3

Cited by 2,861 publications

(480 citation statements)

References 35 publications

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“…It has been well demonstrated that p53 could mediate transcriptional activation of Bax and trigger mitochondrial apoptosis (Toshiyuki et al, 1995;Chipuk et al, 2004). Accordingly, in our study, increase of Bax expression and mitochondrial translocation was inhibited by transfecting with p53 siRNA even though p53 siRNA cannot completely knockdown the expression of p53.…”

Section: Discussionmentioning

confidence: 46%

Emodin-Provoked Oxidative Stress Induces Apoptosis in Human Colon Cancer HCT116 Cells through a p53-Mitochondrial Apoptotic Pathway

Xie¹,

Ma²,

Ma³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 46%

Emodin-Provoked Oxidative Stress Induces Apoptosis in Human Colon Cancer HCT116 Cells through a p53-Mitochondrial Apoptotic Pathway

Xie¹,

Ma²,

Ma³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…33 After translocation to the nucleus, the phosphorylated p53 would enhance Bax gene transcription. 34 Bax translocates to the mitochondria and binds the antiapoptotic proteins Bcl-2 and Bcl-xL and inhibits their protective actions on gate-keeping, ultimately leading to mitochondrial dysfunction and activation of caspase-3. Our data on increased Bax and caspase-3 expression combined with decreased Bcl-xL expression in RPT of diabetic Tg mice lend support to this notion.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Angiotensinogen Increases Tubular Apoptosis in Diabetes

Liu

Brezniceanu²,

Wei³

et al. 2008

Journal of the American Society of Nephrology

144

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The intrarenal renin-angiotensin system (RAS) plays an important role in the progression of diabetic nephropathy. We have previously reported that mice overexpressing angiotensinogen in renal proximal tubular cells (RPTC) develop hypertension, albuminuria, and renal injury. Here, we investigated whether activation of the intrarenal RAS contributes to apoptosis of RPTC in diabetes. Induction of diabetes with streptozotocin in these transgenic mice led to significant increases in BP, albuminuria, RPTC apoptosis, and proapoptotic gene expression compared with diabetic nontransgenic littermates. Insulin and/or RAS blockers markedly attenuated these changes. Hydralazine prevented hypertension but not albuminuria, RPTC apoptosis, or proapoptotic gene expression. In vitro, high-glucose medium significantly increased apoptosis and caspase-3 activity in rat immortalized RPTC overexpressing angiotensinogen compared with control cells, and these changes were prevented by insulin and/or RAS blockers. In conclusion, intrarenal RAS activation and high glucose may act in concert to increase tubular apoptosis in diabetes, independent of systemic hypertension. Diabetic nephropathy (DN) is the leading cause of all ESRD in North America, accounting for 45% to 50% of all cases. 1,2 Intensive insulin therapy and chronic treatment with renin-angiotensin system (RAS) blockers are effective in retarding DN progression but do not provide a cure. [3][4][5] The local intrarenal RAS is well accepted. 6,7 Renal proximal tubular cells (RPTC) express all components of the RAS. 8 -10 Angiotensin II (Ang II) levels and RAS genes are elevated in the kidneys of diabetic rats and humans, 11-13 implying an important role for the intrarenal RAS in DN progression.Glomerular changes in DN first consist of hypertrophy and, later, thickening of the glomerular basement membrane, followed by expansion of the mesangial matrix and glomerulosclerosis. 14 -16 However, the gradual decline of renal function in later stages of DN is invariably associated with tubular atrophy and interstitial fibrosis, hallmarks of ESRD. 17,18 In fact, tubular atrophy and interstitial fibrosis are closely associated with loss of renal function and appear to be better predictors of renal disease progression than glomerular pathology. 15-18 Tubular atrophy in DN is incompletely understood, although apoptosis is a candidate mechanism. Indeed, apoptosis has been detected in RPTC of diabetic mouse, rat, and human kidneys. 19 -24

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“…In the presence of DNA damage p53 may ac vate the ini ator caspase-2 via PIDD [1076,1077]. p53-controlled mitochondrial proteins with pro-apopto c proper es are, for example, the Bcl-2 related proteins Bax, Noxa, PUMA (p53-upregulated modulator of apoptosis) and others [1070,1078,1079].…”

Section: Endogenous Mechanism Of Ac Va On Of Apoptosismentioning

confidence: 99%

DNA repair systems

Chakarov¹,

Petkova²,

Russev³

2014

Biodiscovery

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This paper provides detailed insight into the mechanisms of repair of different types of DNA damage and the direct molecular players (enzymes repairing the damage or tagging the damaged site for further processing; damage sensor molecules; other signalling and effector molecules). The gene c bases of diseases and condi ons associated with defec ve DNA repair are comprehensively reviewed, from the 'classic' severe diseases such as xeroderma pigmentosum and Cockayne syndrome to the much more subtle UV sensi vity syndromes. The review analyses the basic molecular mechanisms underlying the rela vely rare monogenic diseases of DNA repair and management of genome integrity as well as the common mul factorial diseases and condi ons with late onset that are associated with increased levels of oxida ve stress (metabolic syndrome, diabetes type 2, cardiovascular disease) and with accumula on of 'errors' in DNA (normal and pathological ageing phenotypes, various cancers). The role of cell cycle checkpoints in dividing cells and the mechanisms of decision-making for the fate of a damaged cell are discussed with regards to the cell homeostasis in normal and cancerous ssues. The role of major DNA damageassociated signalling and effector molecules (p53, ATM, poly-(ADP-ribose)-polymerase, DNA-dependent protein kinase, BRCA proteins, re noblastoma protein, and others) is discussed and illustrated with examples in the context of health and disease. DNA repair and programmed cell death are viewed together as a unified mechanism for limi ng the presence of damaged cells and cells with poten ally oncogenic transforma on in mul cellular organisms. Special a en on is paid to ageing as a natural phenomenon and an adap ve evolu onary mechanism, with a brief outline of 'successful ageing'. The differen al rates of repair of DNA in transcribed and nontranscribed regions of the genome and the specifici es of DNA repair profile in some types of cells (terminally differen ated cells, pluripotent stem cells, etc.) and in certain taxonomic groups (e.g. 'the rodent repairadox') are discussed with regards to replica ve ageing and the evolu onary processes on microand macroscale. The role of mutagenesis as a 'hit and miss' mechanism and the 'leakiness' of DNA repair for increasing gene c diversity in the course of individual life and on evolu onary scale and the phenomenology of ongoing molecular evolu on are extensively reviewed. Conflict of Interests:No poten al conflict of interest was disclosed by any of the authors. Types of DNA repair systemsIf you wish for peace, prepare for war.Publius Flavius Vege us Renatus, De Re Militari (circa 380 AD).DNA damage is a very broad term, encompassing many different types of lesions in DNA.Accordingly, DNA repair comprises many different types of pathways and mechanisms covering virtually every possible type of injury to the sequence or the structure of DNA.Accep ng Lewin's defini on of DNA damage "... any change that introduces a devia on from the usual double-helical structure" [1] , we may pre...

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Tumor suppressor p53 is a direct transcriptional activator of the human bax gene

Cited by 2,861 publications

References 35 publications

Emodin-Provoked Oxidative Stress Induces Apoptosis in Human Colon Cancer HCT116 Cells through a p53-Mitochondrial Apoptotic Pathway

Emodin-Provoked Oxidative Stress Induces Apoptosis in Human Colon Cancer HCT116 Cells through a p53-Mitochondrial Apoptotic Pathway

Overexpression of Angiotensinogen Increases Tubular Apoptosis in Diabetes

DNA repair systems

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