МАГНИТНЫЕ ИЗОТОПНЫЕ ЭФФЕКТЫ В МЕТАЛЛ-ЗАВИСИМОМ ФЕРМЕНТАТИВНОМ КАТАЛИЗЕ. История

Содержание

1. МАГНИТНЫЕ ИЗОТОПНЫЕ ЭФФЕКТЫ В МЕТАЛЛ-ЗАВИСИМОМ ФЕРМЕНТАТИВНОМ КАТАЛИЗЕ. История
2. Mg and Ca Isotopes Natural Abundance
3. Mg and Zn Isotopes Natural Abundance
4. THE CREATINE KINASE ACTIVE SITE NANOTOPOLOGY
5. Слайд 5
6. The rate of ATP formation by mitochondria
7. Слайд 7
8. ION – RADICAL PAIRS FORMATION (SINGLET
9. Phosphoglycerate kinase
10. The GPK reaction ion-radical mechanism
11. Zeeman interactionFermi interactionMicrowavesP = f [H,ai, n,
12. Слайд 12
13. Слайд 13
14. Слайд 14
15. Buckminsterfullerene(C60)-2-(butadiene-1-yl)--tetra(o--aminobutyryl-o-phtalyl)porphyrinPORPHYLLERENE – MC16
16. Слайд 16
17. PMC16 CATIONITE PROPERTIES AND THE NANOCLUSTERS FORMATION
18. THE CELL COMPARTMENT RETAINING DISTRIBUTION OF [59Fe]PMC16
19. Слайд 19
20. AN AFFINITY CHEROMATOGRAPHY OF THE HUMAN MYOCARDIAL MITOCHONDRIA MEMBRANE PROTEINS ON THE COLUMN WITH AGAROSE-6B-CL-[C17]-PMC16
21. Слайд 21
22. Слайд 22
23. Слайд 23
24. Слайд 24
25. CK Relative ActivityMg2+InfluxFree Protons ExcessSYNERGISM OF THE
26. SYNERGISM OF THE ATP YIELD, OXYGEN CONSUMPTION
27. Слайд 27
28. ADBCELECTRON TRANSMITTING MICROPHOTOGRAMS OF THE RAT MYOCARDIOCYTIC
29. DXR – INDUCED MITOCHONDRIAL DISPLASIA IN RABBIT
30. DXR – INDUCED NUCLEAR DISPLASIA IN RABBIT
31. FRAGMENTATION OF THE RABBIT MYOCARDIOCYTES MITOCHONDRIA IN
32. FRAGMENTATION OF THE RABBIT MYOCARDIOCYTES MITOCHONDRIA IN
33. Слайд 33
34. THE EFFECT OF A PMC16 – TARGETED
35. THE PORPHYLLEREN – MC16 (PMC16) PRE –
36. PMC16 CLUSTER POSITIONING INSIDE THE RAT MYOCARDIOCYTIC
37. Слайд 37
38. Слайд 38
39. Слайд 39
40. THE HYPOXIA-AFFECTED PMC16 METABOLIC DECAY IN RATTHE
41. A HIGHLY SELECTIVE TRAGETING OF PMC16 NANOPARTICELS
42. NOTE: DXR, 20 mg/kg/24 hrs, i.v.: MNA, 10 mg/kg/24 hrs, i.v.:
43. Слайд 43
44. Слайд 44
45. Слайд 45
46. Слайд 46
47. Слайд 47
48. Слайд 48
49. Слайд 49
50. Слайд 50
51. Слайд 51
52. SDS-PAGE: HL-60 Cell DNA Polymerase β66.5 кДа
53. Слайд 53
54. Слайд 54
55. Слайд 55
56. *,25 MgCl2*,43 СаCl2*,67 ZnCl2PMC 16 PMC
57. Слайд 57
58. MIE Impact on the HL-60 cell DNApolβ catalytic activityE, [3H]cpmDNA/mg enzyme
59. MIE Impact on the HL-60 cell DNApolβ catalytic activityE, [3H]cpmDNA/mg enzyme
60. MIE Impact on the HL-60 cell DNApolβ catalytic activityE, [3H]cpmDNA/ mg enzymeE, [3H]cpmDNA/mg enzyme
61. The rate of DNA replication as a
62. The rate of DNA replication as a
63. The rate of DNA replication as a
64. Слайд 64
65. Слайд 65
66. Слайд 66
67. Слайд 67
68. Слайд 68
69. Слайд 69
70. Слайд 70
71. Слайд 71
72. Слайд 72
73. Слайд 73
74. PMC1625Mg2+PMC 16 PMC 1625Mg2+25Mg2+CK, αPGK, PK, ATPsynthase
75. Jorg Pedersen, South Denmark University, Biophisical enzymology
76. Слайд 76
77. Слайд 77
78. Слайд 78
79. Слайд 79
80. Grazie per l’attenzione!
81. Скачать презентанцию

Mg and Ca Isotopes Natural Abundance

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МАГНИТНЫЕ ИЗОТОПНЫЕ ЭФФЕКТЫ В МЕТАЛЛ-ЗАВИСИМОМ ФЕРМЕНТАТИВНОМ КАТАЛИЗЕ. История

Слайды и текст этой презентации

Слайд 1
МАГНИТНЫЕ ИЗОТОПНЫЕ ЭФФЕКТЫ
В МЕТАЛЛ-ЗАВИСИМОМ
ФЕРМЕНТАТИВНОМ КАТАЛИЗЕ.
История вопроса,

достижения и перспективы практического применения.

Кузнецов Д.А.

Кафедра медицинских нанобиотехнологий
МБФ

РНИМУ им. Н.И. Пирогова,
Отдел строения вещества Института химической физики им. Н.Н. Семёнова РАН.

www.rsmu.ru
2015

МАГНИТНЫЕ ИЗОТОПНЫЕ ЭФФЕКТЫ В МЕТАЛЛ-ЗАВИСИМОМ ФЕРМЕНТАТИВНОМ КАТАЛИЗЕ. История вопроса, достижения и перспективы практического применения. Кузнецов Д.А.Кафедра медицинских

Слайд 2Mg and Ca Isotopes Natural Abundance

Слайд 3Mg and Zn Isotopes Natural Abundance

Слайд 4THE CREATINE KINASE ACTIVE SITE NANOTOPOLOGY

Слайд 6The rate of ATP formation by mitochondria (A) and by

creatine
kinase (B) as a function of magnesium isotope
The

yield of ATP is given in mmole/g total protein

intact mitochondria

mitochondria subjected to a selective blockade of oxidative
phosphorylation by 1-methylnicotine amide.

The rate of ATP formation by mitochondria (A) and by creatine kinase (B) as a function of

Слайд 8ION – RADICAL PAIRS FORMATION
(SINGLET – TRIPLET PATH

SHIFT)
MECHANISM
OF THE 25Mg MAGNETIC ISOTOPE EFFECT
EXPRESSED
IN

A BIOLOGICAL PHOSPHORYLATION PRECESSES
(Mt-CK)

ION – RADICAL PAIRS FORMATION (SINGLET – TRIPLET PATH SHIFT) MECHANISM OF THE 25Mg MAGNETIC ISOTOPE

Слайд 9Phosphoglycerate kinase

Слайд 10The GPK reaction ion-radical mechanism

Слайд 11Zeeman interaction
Fermi interaction
Microwaves
P = f [H,ai, n, In, mI, HI,

, J]
m
w
R R
R R
RR
.
.
T
S

Zeeman interactionFermi interactionMicrowavesP = f [H,ai, n, In, mI, HI, , J] mwR RR

Слайд 15Buckminsterfullerene(C60)-2-(butadiene-1-yl)-
-tetra(o--aminobutyryl-o-phtalyl)porphyrin
PORPHYLLERENE – MC16

Слайд 17PMC16 CATIONITE PROPERTIES AND THE NANOCLUSTERS FORMATION AS A FUNCTION

OF pH
Blue arrow shows the

iron-dextrane sphere exclusion limit

1.15nm

14.8nm

6.4nm

10.2nm

3.2nm

4.7nm

, portion of the total PMC16 magnesium

Blue arrow shows the iron-dextrane sphere exclusion limit

PMC16 CATIONITE PROPERTIES AND THE NANOCLUSTERS FORMATION AS A FUNCTION OF pH Blue

Слайд 18THE CELL COMPARTMENT RETAINING DISTRIBUTION OF [59Fe]PMC16 CAUSED BY A

SINGLE i.v. ADMINISTRATION IN RATS
(30 mg/kg, 470-520 Ci/kg).

THE CELL COMPARTMENT RETAINING DISTRIBUTION OF [59Fe]PMC16 CAUSED BY A SINGLE i.v. ADMINISTRATION IN RATS(30 mg/kg, 470-520

Слайд 20AN AFFINITY CHEROMATOGRAPHY OF THE HUMAN MYOCARDIAL MITOCHONDRIA MEMBRANE PROTEINS

ON THE COLUMN WITH AGAROSE-6B-CL-[C17]-PMC16

Слайд 25CK Relative Activity
Mg2+Influx
Free Protons Excess
SYNERGISM OF THE MITOCHONDRIAL MATRIX CK

ACTIVITY, MAGNESIUM CATIONS INFLUX AND THE FREE PROTONS EXCESS DEGREE
The

isolated rat myocardium mitochondria tested.
Yellow / Red stands for the spinless / spin Mg isotopes ratio.

CK Relative ActivityMg2+InfluxFree Protons ExcessSYNERGISM OF THE MITOCHONDRIAL MATRIX CK ACTIVITY, MAGNESIUM CATIONS INFLUX AND THE FREE

Слайд 26SYNERGISM OF THE ATP YIELD, OXYGEN CONSUMPTION AND THE Mg2+

INFLUX IN THE PERFUSED ISOLATED RABBIT HEART MUSCLE TISSUE
ATP yield,

Y/Yo

O2 Consumption

Mg2+ Influx

ATP yield, Y/Yo

O2 Consumption

Mg2+ Influx

A – Zero spin magnesium test B – Magnetic magnesium test

Слайд 28A
D
B
C
ELECTRON TRANSMITTING MICROPHOTOGRAMS OF THE RAT MYOCARDIOCYTIC PERINUCLEAR AREAS
A,

C – PMC16 related hypoxia preventing effect
B – Inhalation oxygen

deficiency hypoxia model
D – Intact myocardium

ADBCELECTRON TRANSMITTING MICROPHOTOGRAMS OF THE RAT MYOCARDIOCYTIC PERINUCLEAR AREAS A, C – PMC16 related hypoxia preventing effectB

Слайд 29DXR – INDUCED MITOCHONDRIAL DISPLASIA IN RABBIT MYOCARDIOCYTES
(B) Mitochondria (M):

0.2 DL50 PMC16, 6 hrs → 0.5 DL50 DXR, 12

hrs.

Arrow sign points to a matrix
granular destruction

(A) Mitochondria (M): 0.5 DL50 DXR, 12 hrs

25Mg2+

DXR – INDUCED MITOCHONDRIAL DISPLASIA IN RABBIT MYOCARDIOCYTES(B) Mitochondria (M): 0.2 DL50 PMC16, 6 hrs → 0.5

Слайд 30DXR – INDUCED NUCLEAR DISPLASIA IN RABBIT MYOCARDIOCYTES
(B) Nucleus (N):

0.2 DL50 PMC16, 6 hrs → 0.5 DL50 DXR, 12

hrs.

Arrow sign points to a matrix
granular destruction

(A) Nucleus (N):0.5 DL50 DXR, 12 hrs.

25Mg2+

DXR – INDUCED NUCLEAR DISPLASIA IN RABBIT MYOCARDIOCYTES(B) Nucleus (N): 0.2 DL50 PMC16, 6 hrs → 0.5

Слайд 31FRAGMENTATION OF THE RABBIT MYOCARDIOCYTES MITOCHONDRIA IN THE DXR-INDUCED ACUTE

HYPOXIA
0.8 DL50 DXR, 20 min (i.v.)
0.8 DL50 DXR, 4

hrs (i.v.)
0.8 DL50 DXR, 12 hrs (i.v.)
0.2 DL50 PMC16, 10 hrs (i.v.)→ DL50 DXR, 12 hrs (i.v.)

FRAGMENTATION OF THE RABBIT MYOCARDIOCYTES MITOCHONDRIA IN THE DXR-INDUCED ACUTE HYPOXIA0.8 DL50 DXR, 20 min (i.v.) 0.8

Слайд 32FRAGMENTATION OF THE RABBIT MYOCARDIOCYTES MITOCHONDRIA IN THE 1-METHYLNICOTINE AMIDE

(MNA) – INDUCED ACUTE HYPOXIA
1.0 DL50 MNA, 6 HRS

(i.v.)
(b) 1.0 DL50 MNA, 12 hrs (i.v.)
(c) 1.0 DL50 MNA, 24 hrs (i.v.)

FRAGMENTATION OF THE RABBIT MYOCARDIOCYTES MITOCHONDRIA IN THE 1-METHYLNICOTINE AMIDE (MNA) – INDUCED ACUTE HYPOXIA 1.0 DL50

Слайд 34THE EFFECT OF A PMC16 – TARGETED DELIVERY OF Mg2+

ON THE DOXORUBICIN (DXR) PRE – SUPPRESSED ATP PRODUCTION IN

RAT MYOCARDIUM

0.8 DL50 DXR, i.v., 6 hrs → PMC16, i.v., 6 hrs

THE EFFECT OF A PMC16 – TARGETED DELIVERY OF Mg2+ ON THE DOXORUBICIN (DXR) PRE – SUPPRESSED

Слайд 35THE PORPHYLLEREN – MC16 (PMC16) PRE – CLINICAL TRIAL
Screen in Safety

and Hazard Assessment
Drug Efficiency Studies
The Tissue Specific Drug Reception Studies
Interaction

with Other Drugs in vivo

OPTIMAL PHARMACOTHERAPY RECOMMENDATIONS

A comparative study on the PMC16 directed delivery / release for Mg2+, Mn2+, Zn2+, Cu2+, Mo2+, Co2+

THE PORPHYLLEREN – MC16 (PMC16) PRE – CLINICAL TRIAL Screen in Safety and Hazard AssessmentDrug Efficiency StudiesThe

Слайд 36PMC16 CLUSTER POSITIONING INSIDE THE RAT MYOCARDIOCYTIC MITOCHONDRIAL MEMBRANE IN

METABOLIC ACIDOSIS (a, c) AND IN NORMAL CONDITIONS (b, d)

a, b – Laser contrast (Nanofinder-S-6A) images
C, d – Confocal scanning microscopy

PMC16 CLUSTER POSITIONING INSIDE THE RAT MYOCARDIOCYTIC MITOCHONDRIAL MEMBRANE IN METABOLIC ACIDOSIS (a, c) AND IN NORMAL

Слайд 40THE HYPOXIA-AFFECTED PMC16 METABOLIC DECAY IN RAT
THE DRUG 59Fe LOSS

DEGREE (—)
HEPATIC OXYGEN COMSUMPTION,
fraction of control
THE DRUG HEPATIC DEACETYLATION DEGREE

(―)

A – Chemically Induced Hypoxia
(0.005-0.5 DL50 MNA, 12 hrs);

B – Oxygen Depleted Inhalation
Hypoxia (15%, O2, 1-10 days)

$THE HYPOXIA-AFFECTED PMC16 METABOLIC DECAY IN RATTHE DRUG 59Fe LOSS DEGREE (—)HEPATIC OXYGEN COMSUMPTION,fraction of controlTHE DRUG$

Слайд 41A HIGHLY SELECTIVE TRAGETING OF PMC16 NANOPARTICELS TOWARDS THE RAT

HEART MUSCLE IN A COURSE OF THE LONG – TERM

ADMINISTRATION OF AN EXTRA LOW DRUG DOSAGE

A HIGHLY SELECTIVE TRAGETING OF PMC16 NANOPARTICELS TOWARDS THE RAT HEART MUSCLE IN A COURSE OF THE

Слайд 42NOTE: DXR, 20 mg/kg/24 hrs, i.v.:

MNA, 10 mg/kg/24 hrs, i.v.:

Слайд 51

CATALYTIC ACTIVITY OF THE BETA-LIKE DNA POLYMERASE FROM HL60

CELLS CHROMATIN AFFECTED BY INHIBITORS AND BY HIGH CONCENTRATION OF POTASSIUM CHLORIDE

Слайд 52SDS-PAGE: HL-60 Cell DNA Polymerase β
66.5 кДа

Слайд 56

,25 MgCl2
,43 СаCl2
*,67 ZnCl2
PMC 16
PMC 16 -

Mg
PMC 16 - Ca
PMC 16 - *Zn
PMC 16

– 25 Mg
PMC 16 – 43Ca
PMC 16 – 67Zn

Клетки
ОМЛ и РБ

Хроматин

Выделение ДНК- пол β

Определение β - критериев:
MW, ИЭТ, Км, Кcat
200 mM KCl
Ингибиторы
3',5'-ДНКазная активность
Предельный размер процессируемых фрагментов ДНК

МИЭ:
25Mg2+
43Ca2+
67Zn2+

Изотермы аффиности:

Me2+/DNApolβ

ПОИСК И АНАЛИЗ КОРРЕЛЯЦИЙ

Параметры цитометрии,
апоптоз

Цитозоль,
Митохондрии,
Нуклеоплазма,
Хроматин

ИСП – МС: Распределение изотопов Me2+

Структура диссертационного исследования

*,25 MgCl2*,43 СаCl2*,67 ZnCl2PMC 16 PMC 16 - *MgPMC 16 - *CaPMC 16 - *Zn

Слайд 58MIE Impact on the HL-60 cell DNApolβ catalytic activity
E, [3H]cpmDNA/
mg

enzyme

Слайд 59MIE Impact on the HL-60 cell DNApolβ catalytic activity
E, [3H]cpmDNA/
mg

enzyme

Слайд 60MIE Impact on the HL-60 cell DNApolβ catalytic activity
E, [3H]cpmDNA/

mg enzyme

E, [3H]cpmDNA/
mg enzyme

Слайд 61The rate of DNA replication as a function of Mg2+

ion concentration. Tritium radioactivity A is measured as the number

of counts/min/mg of DNA. The contents of 25Mg and 24Mg in Mg2+ ions are 86.8 and 98.6% respectively.

The rate of DNA replication as a function of Mg2+ ion concentration. Tritium radioactivity A is measured

Слайд 62The rate of DNA replication as a function of Mg2+

ion concentration. Tritium radioactivity A is measured as the number

of counts/min/mg of DNA. The contents of 25Mg and 26Mg in Mg2+ ions are 86.8 and 98.6% respectively.

Слайд 63The rate of DNA replication as a function of Zn2+

ion concentration. Tritium radioactivity A is measured as the number

of counts/min/mg of DNA. The content of 67Zn in Zn2+ ions is 00%.

The rate of DNA replication as a function of Zn2+ ion concentration. Tritium radioactivity A is measured

Слайд 74PMC16
25Mg2+
PMC 16
PMC 16
25Mg2+
25Mg2+
CK, αPGK, PK, ATPsynthase
∆[dNTP]↑
Anabolism
Support
Perinuclear Permeases
25Mg2+
Oversaturation
of

dNTP nuclear pool
DNApolβ
Invalid DNA Repair
NUCLEUS
CYTOPLASM
EXTRACELLULAR ENVIRONMENT
КОНЦЕПЦИЯ БУЧАЧЕНКО

– КУЗНЕЦОВА :
Синергизм цитоплазматических и внутриядерных событий,
конвертирующих МИЭ 25Mg в цитостатическое воздействие на клетку опухоли

PMC1625Mg2+PMC 16 PMC 1625Mg2+25Mg2+CK, αPGK, PK, ATPsynthase ∆[dNTP]↑AnabolismSupport Perinuclear Permeases25Mg2+Oversaturationof dNTP nuclear poolDNApolβInvalid DNA Repair NUCLEUSCYTOPLASMEXTRACELLULAR ENVIRONMENTКОНЦЕПЦИЯ

Слайд 75Jorg Pedersen, South Denmark University, Biophisical enzymology department, Denmark, Odense
Nikita

Lukzen, Duke University, laboratory of magnetic biology, USA
William Robinson, Nantes

University, Isotopic research center, France
Nicolas Turro (+), Ron Barthels, Columbia University, USA
Nima Amirshahi, Teheran Medical University, Iran
Xeng Wu, Nankin State University, China
S.A. Roumyantsev, M.A. Orlova, State Research center of gematology, oncology and immunology, Russia
Wolfgang Maret, King’s college of London, UK

Jorg Pedersen, South Denmark University, Biophisical enzymology department, Denmark, OdenseNikita Lukzen, Duke University, laboratory of magnetic biology,

Слайд 80Grazie per l’attenzione!

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МАГНИТНЫЕ ИЗОТОПНЫЕ ЭФФЕКТЫ В МЕТАЛЛ-ЗАВИСИМОМ ФЕРМЕНТАТИВНОМ КАТАЛИЗЕ. История

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Слайды и текст этой презентации

Слайд 1МАГНИТНЫЕ ИЗОТОПНЫЕ ЭФФЕКТЫ В МЕТАЛЛ-ЗАВИСИМОМ ФЕРМЕНТАТИВНОМ КАТАЛИЗЕ. История вопроса,

достижения и перспективы практического применения. Кузнецов Д.А.Кафедра медицинских нанобиотехнологий МБФ

Слайд 2Mg and Ca Isotopes Natural Abundance

Слайд 3Mg and Zn Isotopes Natural Abundance

Слайд 4THE CREATINE KINASE ACTIVE SITE NANOTOPOLOGY

Слайд 6The rate of ATP formation by mitochondria (A) and by

creatine kinase (B) as a function of magnesium isotope The

Слайд 8ION – RADICAL PAIRS FORMATION (SINGLET – TRIPLET PATH

SHIFT) MECHANISM OF THE 25Mg MAGNETIC ISOTOPE EFFECT EXPRESSED IN

Слайд 9Phosphoglycerate kinase

Слайд 10The GPK reaction ion-radical mechanism

Слайд 11Zeeman interactionFermi interactionMicrowavesP = f [H,ai, n, In, mI, HI,

, J] mwR RR RRR..TS

Слайд 15Buckminsterfullerene(C60)-2-(butadiene-1-yl)--tetra(o--aminobutyryl-o-phtalyl)porphyrinPORPHYLLERENE – MC16

Слайд 17PMC16 CATIONITE PROPERTIES AND THE NANOCLUSTERS FORMATION AS A FUNCTION

OF pH Blue arrow shows the

Слайд 18THE CELL COMPARTMENT RETAINING DISTRIBUTION OF [59Fe]PMC16 CAUSED BY A

SINGLE i.v. ADMINISTRATION IN RATS(30 mg/kg, 470-520 Ci/kg).

Слайд 20AN AFFINITY CHEROMATOGRAPHY OF THE HUMAN MYOCARDIAL MITOCHONDRIA MEMBRANE PROTEINS

ON THE COLUMN WITH AGAROSE-6B-CL-[C17]-PMC16

Слайд 25CK Relative ActivityMg2+InfluxFree Protons ExcessSYNERGISM OF THE MITOCHONDRIAL MATRIX CK

ACTIVITY, MAGNESIUM CATIONS INFLUX AND THE FREE PROTONS EXCESS DEGREEThe

Слайд 26SYNERGISM OF THE ATP YIELD, OXYGEN CONSUMPTION AND THE Mg2+

INFLUX IN THE PERFUSED ISOLATED RABBIT HEART MUSCLE TISSUEATP yield,

Слайд 28ADBCELECTRON TRANSMITTING MICROPHOTOGRAMS OF THE RAT MYOCARDIOCYTIC PERINUCLEAR AREAS A,

C – PMC16 related hypoxia preventing effectB – Inhalation oxygen

Слайд 29DXR – INDUCED MITOCHONDRIAL DISPLASIA IN RABBIT MYOCARDIOCYTES(B) Mitochondria (M):

0.2 DL50 PMC16, 6 hrs → 0.5 DL50 DXR, 12

Слайд 30DXR – INDUCED NUCLEAR DISPLASIA IN RABBIT MYOCARDIOCYTES(B) Nucleus (N):

0.2 DL50 PMC16, 6 hrs → 0.5 DL50 DXR, 12

Слайд 31FRAGMENTATION OF THE RABBIT MYOCARDIOCYTES MITOCHONDRIA IN THE DXR-INDUCED ACUTE

HYPOXIA0.8 DL50 DXR, 20 min (i.v.) 0.8 DL50 DXR, 4

Слайд 32FRAGMENTATION OF THE RABBIT MYOCARDIOCYTES MITOCHONDRIA IN THE 1-METHYLNICOTINE AMIDE

(MNA) – INDUCED ACUTE HYPOXIA 1.0 DL50 MNA, 6 HRS

Слайд 34THE EFFECT OF A PMC16 – TARGETED DELIVERY OF Mg2+

ON THE DOXORUBICIN (DXR) PRE – SUPPRESSED ATP PRODUCTION IN

Слайд 35THE PORPHYLLEREN – MC16 (PMC16) PRE – CLINICAL TRIAL Screen in Safety

and Hazard AssessmentDrug Efficiency StudiesThe Tissue Specific Drug Reception StudiesInteraction

Слайд 36PMC16 CLUSTER POSITIONING INSIDE THE RAT MYOCARDIOCYTIC MITOCHONDRIAL MEMBRANE IN

METABOLIC ACIDOSIS (a, c) AND IN NORMAL CONDITIONS (b, d)

Слайд 40THE HYPOXIA-AFFECTED PMC16 METABOLIC DECAY IN RATTHE DRUG 59Fe LOSS

DEGREE (—)HEPATIC OXYGEN COMSUMPTION,fraction of controlTHE DRUG HEPATIC DEACETYLATION DEGREE

Слайд 41A HIGHLY SELECTIVE TRAGETING OF PMC16 NANOPARTICELS TOWARDS THE RAT

HEART MUSCLE IN A COURSE OF THE LONG – TERM

Слайд 42NOTE: DXR, 20 mg/kg/24 hrs, i.v.:

MNA, 10 mg/kg/24 hrs, i.v.:

CATALYTIC ACTIVITY OF THE BETA-LIKE DNA POLYMERASE FROM HL60

Слайд 52SDS-PAGE: HL-60 Cell DNA Polymerase β66.5 кДа

Слайд 56 *,25 MgCl2*,43 СаCl2*,67 ZnCl2PMC 16 PMC 16 -

*MgPMC 16 - *CaPMC 16 - *Zn PMC 16

Слайд 58MIE Impact on the HL-60 cell DNApolβ catalytic activityE, [3H]cpmDNA/mg

enzyme

Слайд 59MIE Impact on the HL-60 cell DNApolβ catalytic activityE, [3H]cpmDNA/mg

enzyme

Слайд 60MIE Impact on the HL-60 cell DNApolβ catalytic activityE, [3H]cpmDNA/

mg enzymeE, [3H]cpmDNA/mg enzyme

Слайд 61The rate of DNA replication as a function of Mg2+

ion concentration. Tritium radioactivity A is measured as the number

Слайд 62The rate of DNA replication as a function of Mg2+

ion concentration. Tritium radioactivity A is measured as the number

Слайд 63The rate of DNA replication as a function of Zn2+

ion concentration. Tritium radioactivity A is measured as the number

Слайд 74PMC1625Mg2+PMC 16 PMC 1625Mg2+25Mg2+CK, αPGK, PK, ATPsynthase ∆[dNTP]↑AnabolismSupport Perinuclear Permeases25Mg2+Oversaturationof

dNTP nuclear poolDNApolβInvalid DNA Repair NUCLEUSCYTOPLASMEXTRACELLULAR ENVIRONMENTКОНЦЕПЦИЯ БУЧАЧЕНКО

Слайд 75Jorg Pedersen, South Denmark University, Biophisical enzymology department, Denmark, OdenseNikita

Lukzen, Duke University, laboratory of magnetic biology, USAWilliam Robinson, Nantes

Слайд 80Grazie per l’attenzione!

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МАГНИТНЫЕ ИЗОТОПНЫЕ ЭФФЕКТЫ
В МЕТАЛЛ-ЗАВИСИМОМ
ФЕРМЕНТАТИВНОМ КАТАЛИЗЕ.
История вопроса,

достижения и перспективы практического применения.

Кузнецов Д.А.

Кафедра медицинских нанобиотехнологий
МБФ

creatine
kinase (B) as a function of magnesium isotope
The

Слайд 8ION – RADICAL PAIRS FORMATION
(SINGLET – TRIPLET PATH

SHIFT)
MECHANISM
OF THE 25Mg MAGNETIC ISOTOPE EFFECT
EXPRESSED
IN

Слайд 11Zeeman interaction
Fermi interaction
Microwaves
P = f [H,ai, n, In, mI, HI,

, J]
m
w
R R
R R
RR
.
.
T
S

Слайд 15Buckminsterfullerene(C60)-2-(butadiene-1-yl)-
-tetra(o--aminobutyryl-o-phtalyl)porphyrin
PORPHYLLERENE – MC16

OF pH
Blue arrow shows the

SINGLE i.v. ADMINISTRATION IN RATS
(30 mg/kg, 470-520 Ci/kg).

Слайд 25CK Relative Activity
Mg2+Influx
Free Protons Excess
SYNERGISM OF THE MITOCHONDRIAL MATRIX CK

ACTIVITY, MAGNESIUM CATIONS INFLUX AND THE FREE PROTONS EXCESS DEGREE
The

INFLUX IN THE PERFUSED ISOLATED RABBIT HEART MUSCLE TISSUE
ATP yield,

Слайд 28A
D
B
C
ELECTRON TRANSMITTING MICROPHOTOGRAMS OF THE RAT MYOCARDIOCYTIC PERINUCLEAR AREAS
A,

C – PMC16 related hypoxia preventing effect
B – Inhalation oxygen

Слайд 29DXR – INDUCED MITOCHONDRIAL DISPLASIA IN RABBIT MYOCARDIOCYTES
(B) Mitochondria (M):

Слайд 30DXR – INDUCED NUCLEAR DISPLASIA IN RABBIT MYOCARDIOCYTES
(B) Nucleus (N):

HYPOXIA
0.8 DL50 DXR, 20 min (i.v.)
0.8 DL50 DXR, 4

(MNA) – INDUCED ACUTE HYPOXIA
1.0 DL50 MNA, 6 HRS

Слайд 35THE PORPHYLLEREN – MC16 (PMC16) PRE – CLINICAL TRIAL
Screen in Safety

and Hazard Assessment
Drug Efficiency Studies
The Tissue Specific Drug Reception Studies
Interaction

Слайд 40THE HYPOXIA-AFFECTED PMC16 METABOLIC DECAY IN RAT
THE DRUG 59Fe LOSS

DEGREE (—)
HEPATIC OXYGEN COMSUMPTION,
fraction of control
THE DRUG HEPATIC DEACETYLATION DEGREE

Слайд 52SDS-PAGE: HL-60 Cell DNA Polymerase β
66.5 кДа

Слайд 56

,25 MgCl2
,43 СаCl2
*,67 ZnCl2
PMC 16
PMC 16 -

Mg
PMC 16 - Ca
PMC 16 - *Zn
PMC 16

Слайд 58MIE Impact on the HL-60 cell DNApolβ catalytic activity
E, [3H]cpmDNA/
mg

Слайд 59MIE Impact on the HL-60 cell DNApolβ catalytic activity
E, [3H]cpmDNA/
mg

Слайд 60MIE Impact on the HL-60 cell DNApolβ catalytic activity
E, [3H]cpmDNA/

mg enzyme

E, [3H]cpmDNA/
mg enzyme

Слайд 74PMC16
25Mg2+
PMC 16
PMC 16
25Mg2+
25Mg2+
CK, αPGK, PK, ATPsynthase
∆[dNTP]↑
Anabolism
Support
Perinuclear Permeases
25Mg2+
Oversaturation
of

dNTP nuclear pool
DNApolβ
Invalid DNA Repair
NUCLEUS
CYTOPLASM
EXTRACELLULAR ENVIRONMENT
КОНЦЕПЦИЯ БУЧАЧЕНКО

Слайд 75Jorg Pedersen, South Denmark University, Biophisical enzymology department, Denmark, Odense
Nikita

Lukzen, Duke University, laboratory of magnetic biology, USA
William Robinson, Nantes